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To evaluate long-term oncological and renal function outcomes in patients treated with robot-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC).Patients undergoing RAPN for clinically localized RCC between January 2014 and December 2019 at a tertiary robotic reference center were evaluated. Clinical course, pathologic characteristics, and long-term outcomes were obtained from our institutional review board-approved RCC database.A total of 234 patients were available for analysis. Median follow-up was 46 months (10.8-97.8 months), with 77 patients (32.9%) having at least 5-years of follow-up. Pathology revealed clear-cell RCC in 67.5% (n = 158). Among unfavorable factors, nuclear grades 3 or 4 were found in 67 (29.4%), lymphovascular invasion in 10 (4.3%), positive surgical margins in 22 (9.4%), necrosis in 21 (9%), and sarcomatoid pattern in 2 patients (0.9%). At 12 months, mean serum creatinine was 1.04 mg/dL and 12.9% of patients experienced upstaging in chronic kidney disease. Overall recurrence-free survival at 5-years was 97.8%. There were five local (2.1%) and two distant (0.9%) recurrences, none of them resulting in cancer-specific death. Median time to recurrence was 20 months (11-64 months). Warm ischemia time [hazard ratio (HR) = 1.14, p = 0.034] and sarcomatoid pattern (HR = 124.57, p = 0.001) were the only variables associated with local relapse.Data from this large cohort demonstrate that patients undergoing RAPN have a low incidence of local and distant relapse, resulting in excellent long-term survival while preserving stable renal function in most patients.

Context Urothelial carcinoma can exhibit a wide range of variant morphologies. Many variants present diagnostic challenges and carry clinical implications that inform prognosis and treatment decisions. Objective To provide an overview of the diagnostic, therapeutic, and prognostic significance of histological variants of urothelial carcinoma. Evidence acquisition A PubMed/MEDLINE-based literature search was conducted using the key terms “urothelial carcinoma”, “variant histology”, “nested”, “micropapillary”, “microcystic”, “sarcomatoid”, “squamous differentiation”, “glandular differentiation”, “clear cell”, “plasmacytoid”, “lymphoepithelioma-like carcinoma”, “squamous cell carcinoma”, “small cell carcinoma”, “adenocarcinoma”, “radiotherapy”, “neoadjuvant chemotherapy”, and “adjuvant chemotherapy”. Evidence synthesis The incidence of variant histology is increasing due to improved recognition. Nonetheless, diagnosis can pose challenges due to sampling limitations and interobserver variability. Although associated with advanced disease at presentation, survival outcomes for most variants do not differ significantly compared with pure urothelial carcinoma of the same stage. Controversy exists regarding optimal management due to the low quality of available evidence. For most cases, radical cystectomy with pelvic lymph node dissection (with neoadjuvant chemotherapy when appropriate) represents the standard of care. Small cell carcinoma and lymphoepithelioma-like carcinoma appear to be particularly chemosensitive. Conclusions Accurate identification of variant histological subtypes is an important part of risk stratification, as these variants exhibit aggressive biological behaviour. Variant histology tumours are associated with advanced disease at presentation, which must be considered when counselling patients regarding survival outcomes. Optimal management remains to be defined but in most cases; neoadjuvant chemotherapy and radical cystectomy with pelvic lymph node dissection remains the mainstay of treatment. Patient summary It is important to recognise histological variants of urothelial carcinoma as they indicate aggressive disease. When compared with patients with pure urothelial carcinoma of the same disease stage, survival does not appear to be significantly worse. In most cases, patients with invasive variant histology should be treated with neoadjuvant chemotherapy and radical cystectomy. Take Home Messages Accurate identification of variant histology is important as it exhibits aggressive biological behaviour and affects treatment. Although associated with advanced disease at presentation, with appropriate treatment, survival outcomes are not significantly different compared with pure urothelial carcinoma of the same stage.

Das Urothelkarzinom der Harnblase ist der zweithaufigste urologische Tumor nach dem Prostatakarzinom. Es tritt meistens ab den 6. Lebensjahrzehnt auf und erreicht den Inzidenzhohepunkt im 7. Jahrzehnt. Die Uberlebensrate nach einer Therapie in kurativer Intention hangt vom jeweiligen Tumorstadium ab und liegt zwischen 5 % bei einer metastasierten Erkrankung und uber 90 % bei lokal begrenzten Tumoren. Eine Besonderheit des Urothelkarzinoms der Harnblase ist seine hohe Pravalenz aufgrund haufiger Rezidive kombiniert mit einer relativ niedrigen Letalitat. Die Patienten mussen im Krankheitsverlauf regelmasig uberwacht und eventuell nachbehandelt werden. Dies bedingt immense Kosten fur das Gesundheitssystem. Ausgelost wird das Urothelkarzinom der Harnblase auch durch Umweltgifte. In Kombination mit genetischen Faktoren losen sie vielfaltige molekulare Alterationen der einzelnen Tumorzellen aus. Tabakraucher und Chemiearbeiter haben ein hohes Erkrankungsrisiko. Daneben gehoren schadstoffbelastetes Trinkwasser und eine chronische Zystitis zu den Hauptrisikofaktoren.

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests—PBSn1 and an ancestry-enrichment test—in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10−9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.

Detection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African, and Asian populations. However, populations with Native American ancestry have been largely underrepresented. Here, we used a genome-wide local ancestry enrichment approach complemented with neutral simulations to identify postadmixture adaptations underwent by admixed Chileans through gene flow from Europeans into local Native Americans. The top significant hits (P = 2.4×10−7) are variants in a region on chromosome 12 comprising multiple regulatory elements. This region includes rs12821256, which regulates the expression of KITLG, a well-known gene involved in lighter hair and skin pigmentation in Europeans as well as in thermogenesis. Another variant from that region is associated with the long noncoding RNA RP11-13A1.1, which has been specifically involved in the innate immune response against infectious pathogens. Our results suggest that these genes were relevant for adaptation in Chileans following the Columbian exchange.

To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.

BACKGROUND As alternative for patients that fear genital examination, we assessed adolescent's comfort and ease with self-collected samples for nucleic acid amplification testing for sexually transmitted infections. PATIENTS AND METHODS Sexually active Chilean adolescents and youth under 25 years (174 males and 117 females) were enrolled. Females used self-collected vaginal swabs and males collected first-stream urine. A satisfaction survey evaluating self-sampling system was applied. RESULTS Self-collection was considered easy in 99.3% of the interviewees (CI 95% 0.88-0.98). In women, 79.3% preferred vaginal self-collected samples than pelvic exam (CI 95% 0.73-0.85). In men, 80.3% preferred self-collected first-stream urine to urethral swabs (CI 95% 0.73-0.87). Assuming that self-collected sampling were available, 89.6% of women (CI 95% 0.85-0.94) and 93.2% of men (CI 95% 0.89-0.98) would be prone to be tested more often. Ease of self-collected sampling is not associated with age, gender, educational level or poverty. CONCLUSIONS Chile currently does not have sexually transmitted infections surveillance or screening programs for youth and adolescents. Given self-collected sampling's good acceptability, it could be successfully used when these programs are implemented.

Objective: To generate high-quality data comparing the clinical efficacy and safety profile between monopolar transurethral resection of the prostate (M-TURP) and bipolar plasmakinetic resection of the prostate (PK-TURP) for benign prostatic hyperplasia (BPH). Materials and Methods: Prospective, randomized, single-blinded study conducted in a tertiary-care public institution (Dec/2014-Aug/2016). Inclusion criteria: prostate of

Beyond exposure to arsenic in drinking-water, there is few information about demographic and clinicopathological features of patients with bladder cancer living in arsenic-exposed regions. The aim of the study was to assess the impact of arsenic exposure on clinicopathological characteristics in patients with bladder cancer from a contaminated region compared to those of 2 reference areas.Data of 285 patients with bladder cancer (83 with arsenic exposure from Antofagasta and 202 controls from 2 different sites in Santiago) were obtained through personal interviews and from review of medical records. Demographic, clinicopathological parameters, and information on relevant environmental risk factors were compared with parametric and nonparametric tests as needed. Multivariable analysis was performed to identify independent predictors for high grade and muscle-invasive disease (T2-4).We found no significant differences between groups regarding age at presentation (66.4 vs. 66.5 and 67.2 years; P = 0.69, for exposed vs. the 2 nonexposed groups, respectively) and female gender (28.9% vs. 29.8% and 26.2%; P = 0.84). Proportion of current smokers was significantly lower in the exposed population (10.7% vs. 38.6% and 26.9%; P0.001). There was a significantly higher proportion of locally advanced (10.8 vs. 1.8 and 0.7% T3/4; P = 0.002) and high-grade tumors (79.5% vs. 63.2% and 64.1%; P = 0.001) within arsenic-exposed patients. Arsenic exposure was the only significant predictor for the presence of high-grade tumors (adjusted OR: 5.10; 95%CI: 2.03-12.77) on multivariable analysis.Our study revealed relevant clinical differences in bladder cancer patients with a history of arsenic exposure as compared to nonexposed cases. The more aggressive phenotype associated to arsenic-related bladder cancer should be considered when designing efficient screening strategies for this high-risk population.

Prostate cancer represents the second cancer-related cause of death in North American and Chilean men. The main treatment for incurable stages of disease is surgical or pharmacological castration. However, with time and despite the addition of anti-androgens, the disease progresses to a clinical state that has been commonly referred to as “hormone refractory”. In recent years, the concept of hormone refractoriness has been challenged and replaced by “castration resistance”, acknowledging that further and optimal hormonal manipulation can be attained, beyond achieving testosterone levels at castration range. The purpose of this review is to summarize the recent therapeutic breakthroughs in the management of metastatic castrate resistant prostate cancer (mCRPC), with greater emphasis in the newer hormonal therapy agents such as Abiraterone and Enzalutamide. Future combination and sequential treatment strategies are contextualized in the current era of personalized cancer medicine and genomic characterization of prostate cancer.

Study Objective To determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis infection in sexually active Chilean adolescents and young adults. A comparative analysis was performed between genders to identify demographic, clinical, and sexual behavior characteristics to predict the occurrence of C trachomatis. Design Analytical observational study. Setting Santiago, Chile. Participants Two hundred eighty-six sexually active volunteers aged 24 years or younger (171 female and 115 male); 82.9% (237/286) of them were classified as having high socioeconomic status. Interventions Confidential survey and self-collected samples (urine for men and vaginal swabs for women). Main Outcome Measures Prevalence, demographic characteristics, symptoms, and sexual behavior characteristics. Results The prevalence rate of C trachomatis was 8.7% (10/115) in men and 8.8% (15/171) in women (P = .58). N gonorrhoeae was detected in 1 subject, whereas no T vaginalis cases were detected. In multivariate analysis, having some college education was protective (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.09-0.89), whereas having a higher number of sexual partners was a risk factor (OR, 1.19; 95% CI, 1.1-1.3) for C trachomatis infection. The latter was also predicted by postcoital bleeding (OR, 4.6; 95% CI, 1.30-16.23) in the female model. Conclusion C trachomatis infection rates were similar between both genders. Protective characteristics for the occurrence of this infection were having some college education, lower number of sexual partners, and if female, the absence of postcoital bleeding. This study highlights the importance of C trachomatis screening among the Chilean affluent population younger than 25 years. However, further studies are needed in a more diverse and representative sample to recommend universal screening in Chilean adolescents and young adults.

The conventional technique for percutaneous nephrolithotomy (PNL) ends by placing a nephrostomy tube within the access tract. However, feasibility and safety of tubeless PNL have been widely demonstrated. In this modification, a ureteral stent is usually left in place instead of the nephrostomy tube. The aim of this study is to compare the use of a postoperative indwelling double-J stent versus an overnight-externalized ureteral catheter in patients undergoing tubeless PNL. Sixty-eight patients undergoing tubeless PNL were randomized either for a postoperative double-J stent (group 1) or for an overnight-externalized ureteral catheter (group 2). Outcomes evaluated included postoperative pain, hospital stay length, incidence of hemorrhagic complications, residual lithiasis and urinary leakage. Groups were similar according to age, sex, body mass index and stone burden. There were no significant differences in terms of postoperative pain, incidence of perirenal hematomas, residual lithiasis and urinary leakage. However, patients in group 1 presented longer hospital stays (3.7 ± 1.7 vs. 1.9 ± 0.3 days; p

PURPOSE Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. METHODS Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. RESULTS UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. CONCLUSIONS Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data.A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival.For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P0.001). Patients down-staged at RCpT1 regardless of the use of NAC had the best survival (5-year DSS of 96% vs 45% for those not down-staged; P0.001), while those who were not down-staged despite NAC had 5-year DSS of only 17%.In patients with surgically resectable MPBC, NAC appears to confer benefit to patients with muscle-invasive disease without hydronephrosis, while patients with cT1 disease can proceed to upfront RC. Patients with hydronephrosis do not appear to respond well to NAC and have poor prognosis regardless of treatment paradigm. However, further external validation studies are needed to support the proposed risk stratification before treatment recommendations can be made.

As alternative for patients that fear genital examination, we assessed adolescent's comfort and ease with self-collected samples for nucleic acid amplification testing for sexually transmitted infections.Sexually active Chilean adolescents and youth under 25 years (174 males and 117 females) were enrolled. Females used self-collected vaginal swabs and males collected first-stream urine. A satisfaction survey evaluating self-sampling system was applied.Self-collection was considered easy in 99.3% of the interviewees (CI 95% 0.88-0.98). In women, 79.3% preferred vaginal self-collected samples than pelvic exam (CI 95% 0.73-0.85). In men, 80.3% preferred self-collected first-stream urine to urethral swabs (CI 95% 0.73-0.87). Assuming that self-collected sampling were available, 89.6% of women (CI 95% 0.85-0.94) and 93.2% of men (CI 95% 0.89-0.98) would be prone to be tested more often. Ease of self-collected sampling is not associated with age, gender, educational level or poverty.Chile currently does not have sexually transmitted infections surveillance or screening programs for youth and adolescents. Given self-collected sampling's good acceptability, it could be successfully used when these programs are implemented.

Carcinoma in situ of the urinary tract is a high grade form of nonmuscle invasive urothelial cancer. Our understanding of this entity in the upper tract is poor, and case management remains challenging due to knowledge gaps regarding the definition, diagnosis, treatment options and followup of the disease. We reviewed the available literature for similarities and differences between bladder and upper tract carcinoma in situ, and herein summarize the best available data.We reviewed PubMed® and MEDLINE™ databases from January 1976 through September 2014. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was used to screen publications. All authors participated in the development of a consensus definition of disease.A total of 61 publications were found suitable for this review. All studies were retrospective. Compared to bladder carcinoma in situ, upper tract carcinoma in situ appears to have lower progression rates and improved survival. All available studies demonstrate topical therapy to be effective in treating upper tract carcinoma in situ, with decreased recurrence rates compared to bladder carcinoma in situ. Highlighted areas of current knowledge gaps include variable definitions of disease, methods of drug delivery and ideal treatment course. Improving methods for detection may allow easier diagnosis and more effective treatment.Based on the available data, organ preserving therapy with topical agents is an alternative to radical surgery in select patients with upper tract carcinoma in situ, although this method has not been evaluated in prospective trials. A paradigm shift regarding detection and treatment is needed to improve care and allow better renal preservation. A consensus definition of the disease is offered, and several areas of major knowledge gaps and opportunities for future research are identified.

Objectives Cytology and fluorescence in situ hybridization (FISH) (Urovysion) assay are often used during upper urinary tract surveillance in patients following radical cystectomy with urinary diversion, without much available data regarding efficacy in this population. Here, we evaluate the value of FISH and cytology in detecting upper tract recurrence in the face of a urinary diversion. Materials and methods A review of our cystectomy database revealed 270 patients who had at least one FISH and/or cytology assay performed during surveillance after radical cystectomy. Workup included upper tract imaging in all patients and upper tract endoscopy as indicated. A total of 163 FISH assays and 474 urinary cytology examinations were included in the analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FISH and cytology were assessed. Results Ten patients (3.4%) developed upper tract recurrence after a median follow-up time of 31 months (2–202). All but 1 patient presented either with gross hematuria or positive finding on imaging; 6 had positive FISH and cytology, and 2 had positive cytology only (no FISH done). For detection of upper tract recurrence, sensitivity, specificity, PPV, and NPV of cytology were 80.0%, 85.6%, 10.7%, and 99.5%, respectively; and that for FISH were 85.7%, 86.5%, 23.1%, and 99.2%, respectively. Conclusions The FISH assay and urinary cytology both demonstrate high rates of false positivity and are useful mainly for their negative predictive ability in patients with a urinary diversion. Unless prospective trials show otherwise, both—or at least the more expensive test—can be omitted from surveillance strategies.

OBJECTIVES To determine whether a minimum number of lymph nodes (LNs) exist to detect lymph node invasion (LNI) in patients undergoing radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. METHODS The study included 551 consecutive patients, from 13 centers worldwide, who underwent RNU and lymphadenectomy (LND) between 1992 and 2006. LND was performed at the discretion of the surgeon. All pathological slides were re-reviewed by uropathologists according to strict criteria. Receiver-operating characteristic curve coordinates were used to determine the probability of diagnosing LNI according to the total number of nodes removed. Additionally, the relationship between the number of nodes removed and the rate of positive LNs was tested in univariate and multivariate logistic regression models. RESULTS Median patient age was 68 years (range: 27-97). Of 551 patients, 140 (25.4%) had positive lymph nodes. Median number of lymph nodes removed was 5 (mean 6.7, range 1-41). The Receiver-operating characteristic coordinates plot indicated that the removal of 13 nodes yielded a 90% probability to detect >= 1 positive LNs. The removal of 8 nodes resulted in a 75% probability of finding >= 1 positive nodes. Removal of > 8 LNs (P = .03; odds ratio 1.49) was independently associated with LN1 after adjusting for pathological stage and grade. CONCLUSIONS Our data indicate that 8 LNs need to be removed at radical nephroureterectomy to achieve a 75% probability of finding >= 1 positive nodes. Further improvement of the specificity of LND will require the removal of more lymph nodes. UROLOGY 74: 1070-1077, 2009. (C) 2009 Elsevier Inc.

Background: The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated. Objective: To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC. Design, setting, and participants: The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006. Intervention: Patients were treated with RNU and lymphadenectomy. Measurements: Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified. Results and limitations: in the entire population, the number of LNs removed was not associated with CSM. in univariable (hazard ratio [HR]: 0.99; p = 0.16) or in multi-variable (HR: 0.97; p = 0.12) analyses. In contrast, in the subgroup of pNO patients (n = 412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p = 0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p = 0.004). The inclusion of the variable defining dichotomously the number of removed LNs (= 8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p < 0.001). Conclusions: The extension of the lymphadenectomy in pNO UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background: Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce. Objective: We compared recurrence and cause-specific mortality rates of ONU and LNU. Design, setting, and participants: Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC). Measurements: Univariable and multivariable survival models tested the effect of procedure type (ONU [n = 979] vs LNU [n = 270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, Ureteralcuff management, previous urothelial bladder cancer, and previous endoscopic treatment. Results and limitations: Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p < 0.001) and less lymphovascular invasion (14.8% vs 21.3%, p=0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p=0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p < 0.001] and 2.0 [p = 0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p = 0.1 for both). Conclusions: Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Longterm follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

OBJECTIVE To describe the lymphatic vessel density and to determine the functional and prognostic significance of tumoral lymphatic vessels in upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS The study included 65 patients who had a radical nephroureterectomy (RNU) for UTUC between 1997 and 2004. All pathological slides were re-evaluated by one reference pathologist and clinical data were reviewed. Lymphatic endothelial cells (LECs) were stained immunohistochemically using D2-40. The lymphatic vessel density (LVD) was described in representative intratumoral (ITLVD), peritumoral (PTLVD) and non-tumoral (NTLVD) areas. Random samples were selected for double-immunostaining with D2-40 and CD-34 (to distinguish blood and lymphatic vessels) and the proliferation marker Ki-67 to detect lymphangiogenesis. The primary outcome measures were disease-specific survival (DSS) and disease recurrence (urothelial and/or distant). RESULTS The median (interquartile range) PTLVD was 4.0 (3.0–6.3), and significantly higher than that for ITLVD, of 0.3 (0–1.7) (P

Objectives To determine the predictors of urothelial recurrence, distant metastases, and disease-specific survival (DSS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods The records of 136 patients who underwent RNU in our department between 1983 and 2004 were reviewed. The study population consisted of 116 patients from whom tumor specimens were available for re-evaluation, focusing on pathologic tumor (pT) stage, grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and the presence of significant tumor necrosis. Univariate and multivariate analyses were performed. Results The median follow-up was 38 months (range: 1-193 months). At actual follow-up, 63 patients (56%) were alive and disease-free. Concomitant CIS independently predicted urothelial recurrence ( P = .008). Five-year actual DSS by pT stage was 100% for pTa and pTis, 95% for pT1, 70% for pT2, 54% for pT3, and 14% for pT4 tumors. Disease-specific mortality occurred in 32 patients (28%). A sessile tumor architecture, pT stage, grade, the presence of LVI (all P P = .012), tumor necrosis ( P = .004), and lymph node metastases ( P = .034) were significantly associated with reduced DSS on univariate analysis. Multivariate analysis revealed the presence of LVI ( P P = .023) as independent predictors for reduced DSS. Conclusions RNU provides adequate local control and long-term DSS in patients with localized UTUC. LVI and pT stage are independent predictors for reduced DSS and can be used for the identification of patients who are likely to benefit from adjuvant therapies.

Objectives Aim of the study was to describe and evaluate the association of lymph vessel density with clinicopathological parameters and survival in patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder. Methods The data on 108 patients with muscle-invasive bladder TCC, who underwent radical cystectomy, were reviewed retrospectively. Sections were analysed immunohistochemically for D2-40, a specific lymphatic endothelial cell (LEC) marker. Counts of lymph vessels were taken in intratumoural and peritumoural areas as well as in normal tissue. To detect proliferating LECs, we performed a double immunostaining for D2-40 and the proliferation marker Ki-67. Results Peritumoural vessels were observed in 105 (97.2%) sections and intratumoural vessels in 65 (60.2%). Higher intratumoural lymph vesseI density (LVD) correlated significantly with poor histological differentiation ( p =0.01). Higher peritumoural LVD showed a significant association with the presence of lymph node metastasis ( p =0.0004). However, LVDs had no statistically significant influence on survival. Intratumoural and peritumoural lymph vessels showed proliferating LECs in varying proportions in all examined samples. Conclusions The present study is the first to suggest the existence of proliferating lymph vessels, and, therefore, of lymphangiogenesis in bladder TCC. To our knowledge, it is also the first to confirm a strong correlation of higher peritumoural LVD with the presence of lymph nodes in clinically localized invasive bladder TCC. These findings indicate that lymphangiogenesis may contribute to tumour dissemination and thus provide a potential target for bladder cancer therapy.

Etwa 95 % aller Harnblasenkarzinome haben ihren Ursprung im Urothel. Urotheliale Neoplasien umfassen ein breites Spektrum von Tumoren mit heterogenem Malignitatspotenzial, das durch vielfaltige molekulare Alterationen der Tumorzellen erklart wird. Bei etwa 75 % der Patienten mit einem Urothelkarzinom besteht zum Zeitpunkt der Diagnose ein nichtmuskelinvasiver Tumor. Daruber hinaus gibt es verschiedene Typen von Tumormorphologien, wie z. B. flache (Carcinoma in situ), papillare und solide Tumoren.

INTRODUCTION AND OBJECTIVES: Muscle-invasive urothelial carcinoma of the urinary bladder (UCUB) is an aggressive disease. The standard treatment of care is radical cystectomy (RC). Trimodal bladder-preserving treatment (BPT), including transurethral resection of the bladder tumor, radiation, and chemotherapy has gained considerable interest. We sought to perform a comparative effectiveness assessment of RC vs. BPT in a stage-for-stage analysis. METHODS: We performed a retrospective cohort study of Medicare beneficiaries with non-metastatic muscle-invasive (T2eT4a, N0) UCUB treated with RC or BPT from 1991 to 2009. Following instrumental variable analysis that accounts for both measured and unmeasured confounders, multivariable Coxand competing-risks regression two-stage residual inclusions models were fitted. All analyses were stratified according to disease stage (organ-confined vs. non-organ confined). Our primary outcomes were overall survival (OS) and cancer-specific mortality (CSM). RESULTS: Overall 4168 patients with muscle-invasive UCUB were identified, where 3488 (84%) underwent RC and 680 (16%) received BPT, respectively. During the entire study span, the 5-year OS rates for RC and BPT were 42.9% (95% confidence interval [CI]1⁄441 to 45%) and 21.8% (95% CI1⁄419 to 26%), respectively. Five-year CSM rates were 34.0% (95% CI1⁄432 to 36) and 47.6% (95% CI1⁄444 to 52) for the same groups, respectively. In patients with organ-confined UCUB (T2N0), BPTtreated individuals had significantly increased risks of mortality (hazard ratio [HR]: 1.49, 95% CI1⁄41.04e2.13, P1⁄40.031) and CSM (HR: 1.66, 95% CI1⁄41.03e2.67, P1⁄40.036) compared to RC patients. Among those with non-organ confinedUCUB ( T3N0), no differencewas noted with respect to OS (HR: 1.22, 95%CI1⁄40.62e2.40, P1⁄40.571) and CSM (HR: 1.13, 95% CI1⁄40.48e2.64, P1⁄40.780) between the two groups. CONCLUSIONS: RC was associated with improved cancer control outcomes compared to BPT in organ-confined UCUB. However, no difference between the two treatment modalities was observed with respect to survival amongst patients with more advanced disease stage.

While many urologists recommend radical cystectomy for micropapillary bladder cancer invading the lamina propria (cT1), contradictory small reports exist on the efficacy of conservative management with intravesical bacillus Calmette-Guérin for this disease. We report our updated experience in what to our knowledge is the largest series of patients with cT1 micropapillary bladder cancer.An institutional review board approved review of our cancer database identified 283 patients with micropapillary bladder cancer, including 72 staged with cT1N0M0 disease at diagnosis and initiation of therapy. Survival analysis was performed using the Kaplan-Meier estimator and compared using the log rank test.In this cohort of 72 patients 40 received primary intravesical bacillus Calmette-Guérin and 26 underwent up-front radical cystectomy. Of patients who received bacillus Calmette-Guérin 75%, 45% and 35% experienced disease recurrence, progression and lymph node metastasis, respectively. Patients treated with up-front cystectomy had improved survival compared to patients treated with primary bacillus Calmette-Guérin (5-year disease specific survival 100% vs 60% p = 0.006) and patients who underwent delayed cystectomy after recurrence (5-year disease specific survival 62%, p = 0.015). Prognosis was especially poor in patients who waited for progression before undergoing radical cystectomy with an estimated 5-year disease specific survival of only 24% and a median survival of 35 months. In patients treated with up-front cystectomy pathological up-staging was found in 27%, including 20% with lymph node metastasis.While certain patients with T1 micropapillary bladder cancer may respond to intravesical bacillus Calmette-Guérin, survival is improved in those who undergo early radical cystectomy. Further molecular studies are needed to identify subsets of patients in whom the bladder can be safely spared.

Prostate cancer represents the second cancer-related cause of death in North American and Chilean men. The main treatment for incurable stages of disease is surgical or pharmacological castration. However, with time and despite the addition of anti-androgens, the disease progresses to a clinical state that has been commonly referred to as “hormone refractory”. In recent years, the concept of hormone refractoriness has been challenged and replaced by “castration resistance”, acknowledging that further and optimal hormonal manipulation can be attained, beyond achieving testosterone levels at castration range. The purpose of this review is to summarize the recent therapeutic breakthroughs in the management of metastatic castrate resistant prostate cancer (mCRPC), with greater emphasis in the newer hormonal therapy agents such as Abiraterone and Enzalutamide. Future combination and sequential treatment strategies are contextualized in the current era of personalized cancer medicine and genomic characterization of prostate cancer.

Identification of susceptibility to double-strand breaks (DSBs) may provide valuable information about individual bladder cancer (BC) risk. The formation of γ-H2AX foci is a highly sensitive marker for DNA DSBs induction. We assessed whether levels of γ-H2AX in peripheral blood lymphocytes (PBL) obtained after stimulation by ionizing radiation (IR) are able to predict BC risk. Patients were enrolled from an ongoing BC case-control study. Baseline- and IR-induced H2AX phosphorylation was assessed in PBL from 174 newly diagnosed and untreated BC patients and from 174 matched control subjects by a novel, image-based, high-throughput phenotypic assay. The ratio of γ-H2AX level of IR-treated cells to that of non-treated cells (baseline) was used as the parameter to assess the sensitivity to the mutagen. The mean γ-H2AX ratios were significantly higher for cases than for controls (1.43±0.14 versus 1.35±0.12; P = 8.45×10(-8)). This trend was irrespective of age, sex and smoking status. The risk estimates of BC for induced DSBs by tertile distributions in controls showed also a significant trend for increased risk at the highest tertile for the whole cohort (odds ratio = 5.16; 95% confidence interval = 2.69, 9.89; P = 7.78 × 10(-7)) as well as for each category. Our findings suggest that a higher susceptibility to induction of DSBs as measured by the γ-H2AX assay is significantly associated with an increased risk for BC. This might help to identify individuals at high risk for this cancer, adding new perspectives to established epidemiological and genetic risk factors. Further research of the role of γ-H2AX in biological processes of BC is warranted.

Objective: Carcinoma in situ (OS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). Materials and methods: A multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower. Results: Concomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients. Conclusion: The presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy. (C) 2012 Elsevier Inc. All rights reserved.

In this study we assessed bladder cancer health care and mortality trends in recent decades in a well studied arsenic exposed area in Northern Chile.Arsenic levels in the affected region were obtained for the last 60 years, and correlated with bladder cancer hospital discharge and mortality rates in recent decades.Bladder cancer hospital discharge rates were significantly higher in the affected region (peak RR 3.6, 95% CI 3.0-4.7). Mortality rates for bladder cancer showed a trend of increase during the period analyzed, reaching peak mortality rates of 28.4 per 100,000 for men and 18.7 per 100,000 for women in the last 10 years. Poisson regression models showed an increased mortality risk in the studied region compared to the rest of the country until the present for men (IRR 5.3, 95% CI 4.8-5.8) and women (IRR 7.8, 95% CI 7.0-8.7). Mean age at cancer specific death was significantly lower in the exposed region (69.6 years, 95% CI 68.4-70.7 vs 73.7 years, 95% CI 73.3-74.2, p0.01).Exposure to arsenic is related to a significant need for bladder cancer health care and to high mortality rates even 20 years after having controlled arsenic levels in drinking water. Affected individuals should be aware of the significant impact of this ecological factor. Further research is required to identify strategies for the management of bladder cancer in arsenic exposed populations.

We evaluated antitumoral effect of combined chemotherapy and interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental urothelial bladder cancer (UBC) model. EJ UBC cells were transfected with recombinant IL-12 genes using a liposomal transfection agent. Pirarubicin (THP) was added to the experimental samples at a final concentration of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected cells, untransfected cells plus THP and transfected cells plus THP. Death rates (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model was established by subcutaneous injection of EJ cells to the nude mice. Four groups were assigned in vivo: control group; THP group; IL-12 gene group and IL-12 gene plus THP group. After injection of combined THP and IL-12 gene therapy, tumor size and IL-12 levels were evaluated. In vitro study: DR in the THP + IL-12 gene therapy group (58.2 ± 15.8%) was significantly higher than transfected group (12.2 ± 5.6%; P = 0.01) and untransfected cells plus THP group (33.4 ± 7.8; P = 0.046). A higher amount of apoptotic changes and necrosis on transmission electron microscope analysis were observed in transfected cells plus THP group. In vivo study: A significant tumor attenuation was found in IL-12 gene in combination with THP group when compared with any other groups that were treated without Il-12 or THP (P

Background: Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series. Objective: To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU. Design, setting, and participants: Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as > 10% of the tumour area. Intervention: Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes. Measurements: Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses. Results and limitations: Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p < 0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p = 0.037 and p = 0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%). Conclusions: Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting. (c) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.