Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment.

PURPOSE: The purpose of this American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In 2023, the NMIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from July 2019 to May 2023. This review identified 1918 abstracts, of which 75 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) in support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on variant histologies, urine markers after diagnosis of bladder cancer, intravesical therapy, BCG maintenance, enhanced cystoscopy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer.

OBJECTIVE: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. MATERIALS AND METHODS: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. RESULTS: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CONCLUSION: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

PURPOSE: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. EXPERIMENTAL DESIGN: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. RESULTS: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). CONCLUSION: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Demographic disparities of penile cancer in Appalachian Kentucky.

INTRODUCTION: Appalachian Kentucky is a region characterized by poor healthcare literacy and access. We investigate the disparities in demographic distribution and outcomes of penile squamous cell carcinoma (pSCC) in rural Kentucky. MATERIALS AND METHODS: Data were retrieved for patients with pSCC from 1995-2015 from the Kentucky Cancer Registry and the Surveillance, Epidemiology and End Results Program (SEER) and were used to investigate differences between Appalachian Kentucky and the remainder of the state and country. RESULTS: The incidence of pSCC from 1995-2015 in Appalachian Kentucky was over 60% higher than non-Appalachian regions (2.6 vs. 1.6 cases/100,000 people). Nearly 40% were from Appalachian counties. They presented with similar grade and pT stage at diagnosis but were more likely to have pN+ disease (p < 0.001). Rates of cancer-specific mortality (CSM) were similar between the two regions, but patients with CSM exhibited shorter survival interval from diagnosis in Appalachia (median 20 vs. 26 months, p = 0.016). Compared to national SEER data, patients from Appalachian Kentucky presented with similar grade and stage but exhibited higher rates of CSM (24.0% vs. 20.1%, p = 0.029). African Americans (AA) comprised only 5% of patients but exhibited high pathologic stage at presentation (p = 0.041) and shorter survival intervals (median 12 vs. 23 months, p = 0.023) compared to Caucasians. CONCLUSIONS: There is a disproportionately high rate of pSCC in Appalachian Kentucky. Both Appalachian and AA men exhibited more advanced disease at presentation and shorter survival, identifying socioeconomic and racial disparities which can be targeted to improve outcomes in high risk individuals.

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters.

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.

Predictive value of phenotypic signatures of bladder cancer response to cisplatin-based neoadjuvant chemotherapy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive urothelial carcinoma of the bladder confers only a modest survival advantage. Patients with pathologic progression on NAC have poor outcomes related to a delay in definitive surgical management. OBJECTIVE: To characterize the value of epithelial-mesenchymal transition (EMT) effectors and other novel biomarkers to predict response to NAC. METHODS: A tissue microarray was constructed from patients with clinical stage T2 urothelial carcinoma of the bladder using transurethral resection (TUR) specimens (N = 69) and case-matched post-NAC cystectomy specimens (N = 51). Patients were stratified based on pathologic response to NAC and cancer-specific survival. Biomarker expression in TUR specimens was correlated with pathologic response to NAC and clinical outcomes. Phenotypic changes in expression induced by cisplatin-based NAC were characterized in primary TUR and post-NAC cystectomy and lymph node metastasis specimens. RESULTS: Increased expression of mesenchymal markers and actin-cytoskeleton regulators, as well as low apoptosis index, in TUR specimens was associated with pathologic progression on cisplatin-based NAC. Overexpression of N-cadherin and decreased apoptosis was predictive of disease-specific mortality. NAC decreased cofilin phosphorylation and induced a mesenchymal-epithelial transition phenotype. CONCLUSIONS: The epithelial-mesenchymal transition phenotype and actin-cytoskeleton remodeling are associated with pathologic progression on NAC. Chemotherapy induced an mesenchymal-epithelial transition phenotype and decreased cofilin phosphorylation, providing new insights into therapeutic resistance mechanisms. Primary tumors with high apoptosis rates exhibited favorable response to NAC and lower mortality rates, indicating that these tumors may be sensitized to therapy. Further validation will establish these novel signatures as predictors of therapeutic response.

Root Causes and Modifiability of 30-Day Hospital Readmissions after Radical Cystectomy for Bladder Cancer.

PURPOSE: Radical cystectomy is associated with high complication and rehospitalization rates. An understanding of the root causes of hospital readmissions and the modifiability of factors contributing to readmissions may decrease the morbidity associated with radical cystectomy. We characterize the indications for rehospitalization following radical cystectomy, and determine whether these indications represent immutable patient disease and procedure factors or whether they are modifiable. MATERIALS AND METHODS: From MarketScan® databases we identified patients younger than 65 years with a diagnosis of bladder cancer who underwent radical cystectomy between 2008 and 2011 and were readmitted to the hospital within 30 days of radical cystectomy. All associated ICD-9 codes in the index admission, subsequent outpatient claims and readmission claims were independently reviewed by 3 surgeons to determine a root cause of rehospitalization. Causes were broadly categorized as medical, surgical or infectious, and reviewers determined whether the readmission was modifiable. Multivariate logistical regression models were used to identify factors associated with rehospitalization. RESULTS: A total of 1,163 patients were included in the study and 242 (21%) were readmitted to the hospital within 30 days. Of these readmissions 26% were considered modifiable (kappa=0.71). Of the nonmodifiable readmissions an infectious cause accounted for 52% and a medical cause accounted for 48%, whereas of the modifiable readmissions 62% were due to surgical causes, 30% to medical and 8% to infectious causes. On multivariate analysis only discharge to a skilled nursing facility was associated with modifiable (OR 6.12, 95% CI 2.32-16.14) or nonmodifiable (OR 3.27, 95% CI 1.63-6.53) hospital readmissions. CONCLUSIONS: The majority of rehospitalizations after radical cystectomy are attributable its inherent morbidity. However, optimization of aspects of peri-cystectomy care could minimize the morbidity of radical cystectomy.

Overuse of antimicrobial prophylaxis in community practice urology.

PURPOSE: We examined index urological surgeries to assess utilization patterns of antimicrobial prophylaxis in a large, community based population. MATERIALS AND METHODS: From the Premier Perspectives Database we identified patients who underwent inpatient urological surgeries that are considered index procedures by the ABU (American Board of Urology), including radical prostatectomy, partial or radical nephrectomy, radical cystectomy, ureteroscopy, shock wave lithotripsy, transurethral resection of the prostate, percutaneous nephrostolithotomy, transvaginal surgery, inflatable penile prosthesis, brachytherapy, transurethral resection of bladder tumor and cystoscopy. Procedures were identified based on ICD-9 procedure codes for 2007 to 2012. Antimicrobial administration, class and duration were abstracted from patient billing data. The class and duration of antimicrobials concordant with the 2008 AUA Best Practice Policy Statement was used to determine compliance. RESULTS: The overall compliance rate was 53%, ranging from 0.6% for radical cystectomy to 97% for shock wave lithotripsy. Antimicrobial use consistent with AUA Best Practices included the appropriate class in 67% of cases (range 34% to 80%) and the recommended duration in 78% (range 1.2% to 98%). Average prophylaxis duration for procedures for which it is recommended ranged from 1.1 days after brachytherapy to 10.3 days after radical cystectomy. The compliance rate increased from 46% overall in 2007 to 59% overall in 2012. CONCLUSIONS: We documented considerable variation in antimicrobial prophylaxis for urological surgery. Compliance with AUA Best Practices increased with time but overall rates remain less than 60%. Efforts are needed to better understand the reasons for variation from recommended antimicrobial prophylaxis for common inpatient urological procedures to help decrease resultant complications and improve outcomes.

Neobladders and continent catheterizable stomas for the bladder cancer survivor.

PURPOSE OF REVIEW: Health-related quality of life (HRQOL) following radical cystectomy for bladder cancer is an important outcome measure following radical cystectomy. Understanding HRQOL issues related to continent urinary diversion is crucial in the care and counseling of patients undergoing radical cystectomy. The goals of this review are to give a broad overview of the major types of continent urinary diversions and to review recent literature examining HRQOL in patients undergoing orthotopic neobladders and continent catheterizable urinary reservoirs following radical cystectomy. RECENT FINDINGS: Generic questionnaires that broadly address physical, social, and mental functioning and bladder cancer-specific questionnaires that more specifically address urinary, bowel, and sexual function have been utilized to measure HRQOL following radical cystectomy. Although existing studies indicate that overall quality of life may be similar in patients with continent and noncontinent urinary diversions, more specific comparisons of urinary and sexual function are conflicting and complicated by sex-specific concerns. Uterine preservation may improve urinary function in women with continent urinary diversions. SUMMARY: Although the development of disease-specific validated questionnaires has improved our understanding of HRQOL following radical cystectomy, a lack of prospective studies limits conclusions regarding the superiority of diversion type. Appropriate preoperative consultation may facilitate realistic expectations, thereby optimizing outcomes.

Burden and timing of venothrombolic events in patients younger than 65 years undergoing radical cystectomy for bladder cancer.

INTRODUCTION AND OBJECTIVES: Venothrombolic events (VTEs) following radical cystectomy (RC) are a significant contributor to postoperative morbidity. A better understanding of the incidence and timing of VTE would clarify chemoprophylaxis strategies among RC patients. We sought to characterize the burden of VTE after RC by defining their timing and effect utilizing the MarketScan commercial databases. METHODS: From MarketScan databases, we identified patients younger than 65 years undergoing RC for a primary diagnosis of bladder cancer between 2008 and 2011 with International Classification of Diseases, 9th Edition diagnosis and procedure codes. MarketScan includes inpatient and outpatient health insurance claims of 34 million enrollees annually with data from 150 employers and 13 commercial health plans. We identified the occurrence of VTE, including both pulmonary embolism and deep vein thrombosis, in patients undergoing RC by searching MarketScan for relevant International Classification of Diseases, 9th Edition codes for these diagnoses. Our primary outcome of interest was the timing of VTEs. Multivariate logistical regression models were used to identify patient factors that were associated with VTEs. RESULTS: A total of 1,581 patients were included in our analysis. Overall, 10% of patients experienced VTEs within 90 days of RC. The incidence of postoperative VTEs during the index admission, after discharge and within 30 days of surgery, and between 31 and 90 days postoperatively was 2.9%, 3.8%, and 3.3%, respectively. Prolonged index hospitalization, discharge to a skilled nursing facility, and orthotopic neobladder urinary diversion were significantly associated with VTE within 30 days of RC. CONCLUSION: Most VTEs occur after discharge from the index RC hospitalization. Consideration should be given to extended chemoprophylaxis in this high-risk group of patients.

Use and outcomes of extended antibiotic prophylaxis in urological cancer surgery.

PURPOSE: Although perioperative antibiotic prophylaxis prevents postoperative infectious complications, national guidelines recommend cessation of antibiotics within 24 hours after the procedure. Extended antibiotic prophylaxis beyond 24 hours may contribute to hospital acquired infections such as Clostridium difficile colitis. We evaluated practice patterns of antibiotic prophylaxis in genitourinary cancer surgery and assessed the impact of antibiotic prophylaxis on hospital acquired C. difficile infections. MATERIALS AND METHODS: We identified 59,184 patients treated with radical prostatectomy, 27,921 who underwent partial or radical nephrectomy, and 5,425 treated with radical cystectomy for prostate, kidney and bladder cancers, respectively, from the Premier Perspective Database (Premier Inc., Charlotte, North Carolina) from 2007 to 2012. We constructed hierarchical linear regression models to identify patient and hospital factors associated with extended antibiotic prophylaxis. We evaluated the association between extended antibiotic prophylaxis and C. difficile infections for patients who underwent partial or radical nephrectomy and radical cystectomy with multivariate logistic regression. RESULTS: Surgery specific models demonstrated that hospital identity was associated with a substantial proportion of the variation in extended antibiotic prophylaxis (20% to 35% for radical prostatectomy, partial or radical nephrectomy, and radical cystectomy). Postoperative C. difficile colitis occurred in 0.02% of patients treated with radical prostatectomy, 0.23% of those treated with partial or radical nephrectomy and 1.7% of those treated with radical cystectomy. On multivariate analysis extended antibiotic prophylaxis was associated with higher odds of C. difficile infection after partial or radical nephrectomy (OR 3.79, 95% CI 2.46-5.84) and radical cystectomy (OR 1.64, 95% CI 1.12-2.39). CONCLUSIONS: Antibiotics may be overused after genitourinary cancer surgery and this overuse is associated with hospital acquired C. difficile colitis. Efforts are needed to encourage greater compliance with evidence-based approaches to postoperative care.

Role of maximal endoscopic resection before cystectomy for invasive urothelial bladder cancer.

INTRODUCTION/BACKGROUND: The aim of this study was to examine whether TUR of all visible endophytic tumors performed before RC, with or without NC, affects final pathologic staging. PATIENTS AND METHODS: We retrospectively reviewed data from patients with clinical T2-T4N0-1 urothelial carcinoma of the bladder who underwent RC at our institution between July 2005 and November 2011. Degree of TUR was derived from review of operative reports. We used multivariate logistic regression to assess the association of maximal TUR on pT0 status at time of RC. RESULTS: Of 165 eligible RC patients, 81 received NC. Reported TUR of all visible tumors was performed in 38% of patients who did not receive NC and 48% of NC patients (P = .19). Nine percent of patients who underwent maximal TUR and did not receive NC were pT0, whereas among NC patients, pT0 was seen in 39% and 19% of those with and without maximal TUR, respectively (P = .05). On multivariate analysis in all patients, maximal TUR was associated with a nonsignificant increased likelihood of pT0 status (odds ratio [OR], 2.03; 95% confidence interval [CI], 0.84-4.94), which was significant when we restricted the analysis to NC patients (OR, 3.17; 95% CI, 1.02-9.83). CONCLUSION: Maximal TUR of all endophytic tumors before NC is associated with complete pathologic tumor response at RC. Candidates for NC before RC should undergo resection of all endophytic tumors when feasible. Larger series are warranted to see if maximal TUR leads to improved overall and disease-specific survival.

Chemical management in fungicide sensivity of Mycosphaerella fijiensis collected from banana fields in México

The chemical management of the black leaf streak disease in banana caused by Mycosphaerella fijiensis (Morelet) requires numerous applications of fungicides per year. However this has led to fungicide resistance in the field. The present study evaluated the activities of six fungicides against the mycelial growth by determination of EC50 values of strains collected from fields with different fungicide management programs: Rustic management (RM) without applications and Intensive management (IM) more than 25 fungicide application/year. Results showed a decreased sensitivity to all fungicides in isolates collected from IM. Means of EC50 values in mg L-1 for RM and IM were: 13.25 ± 18.24 and 51.58 ± 46.14 for azoxystrobin, 81.40 ± 56.50 and 1.8575 ± 2.11 for carbendazim, 1.225 ± 0.945 and 10.01 ± 8.55 for propiconazole, 220 ± 67.66 vs. 368 ± 62.76 for vinclozolin, 9.862 ± 3.24 and 54.5 ± 21.08 for fludioxonil, 49.2125 ± 34.11 and 112.25 ± 51.20 for mancozeb. A molecular analysis for β-tubulin revealed a mutation at codon 198 in these strains having an EC50 greater than 10 mg L-1 for carbendazim. Our data indicate a consistency between fungicide resistance and intensive chemical management in banana fields, however indicative values for resistance were also found in strains collected from rustic fields, suggesting that proximity among fields may be causing a fungus interchange, where rustic fields are breeding grounds for development of resistant strains. Urgent actions are required in order to avoid fungicide resistance in Mexican populations of M. fijiensis due to fungicide management practices.

The costs of non-muscle invasive bladder cancer.

Bladder cancer is a common diagnosis, affecting 70,000 Americans each year. Because the diagnosis, management, and long-term follow-up of non-muscle invasive bladder cancer requires advanced imaging and invasive testing, economic evaluations have shown bladder cancer to be the costliest cancer to treat in the US on a per capita basis. Adjunctive tests for surveillance have not obviated the need for cystoscopy and cytology. Indirect costs to patients include loss of work, decreased productivity, and diminished quality of life associated with diagnosis, treatment, and surveillance. Improved value may be achieved with better compliance with evidence-based practices for non-muscle invasive bladder cancer care.

Multifocal pupillography identifies ranibizumab-induced changes in retinal function for exudative age-related macular degeneration.

PURPOSE: To investigate the efficacy of multifocal pupillographic objective perimetry (mfPOP) to quantify the effects of intravitreal ranibizumab injection for choroidal neovascularization (CNV) secondary to exudative age-related macular degeneration (AMD). METHODS: mfPOP visual fields from 20 patients with unilateral exudative AMD treated with intravitreal ranibizumab were measured before and after 3 months of treatment and were compared with that in 30 normal subjects. Two stimulus types consisting of ensembles of 24 or 44 independent stimuli per eye had a mean presentation interval at each region of 1 second. Pupil responses were recorded with video cameras under infrared illumination. Multiple linear models were fitted to contraction amplitudes and delay to peak responses, to determine the independent effects of exudative AMD before and after ranibizumab therapy. RESULTS: After 3 months of treatment, mean additional response delays compared to normal subjects for the 24-region stimulus improved significantly (P < 5 × 10⁻9) from a mean of 18.82 ± 3.0 ms at baseline to 7.45 ± 3.15 ms. The mean effect of exudative AMD at baseline decreased constriction amplitude by -1.11 ± 0.24 dB (P < 0.00001) with little improvement after ranibizumab therapy. Small pretreatment elevations of extrafoveal sensitivity correlated with improvements in central retinal thickness (CRT) after treatment (P < 0.0005). CONCLUSIONS: Improvements in mfPOP contraction amplitudes and time to peak responses were measured in eyes treated with intravitreal ranibizumab; however, response delays appeared to be the most indicative of functional improvement. Confirmation of hypersensitivity in the extrafoveal field in a larger group may support this finding as a prognostic marker for good treatment outcomes.