Lessons from a population-based bladder cancer registry: exploring why survival is not improving.

OBJECTIVE: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades. METHODS: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study. RESULTS: Invasive bladder cancer age-standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non-bladder cancer-specific deaths in older people, there was no change in the bladder cancer-specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not. CONCLUSIONS: Invasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor. PATIENT SUMMARY: We looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously.

Perspectives on technology: to use or to reuse, that is the endoscopic question-a systematic review of single-use endoscopes.

OBJECTIVE: To compare clinical outcomes of single-use endoscopes with those of reusable endoscopes to better define their role within urology. METHODS: A systematic search of electronic databases was performed. All studies comparing the clinical outcomes of participants undergoing urological procedures with single-use endoscopes to those of participants treated with reusable endoscopes were included. Results are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. RESULTS: Twenty-one studies in 3943 participants were identified. Six different single-use flexible ureteroscopes and two different single-use flexible cystoscopes were assessed. There were no differences in mean postoperative infection rates (4.0% vs 4.4%; P = 0.87) or overall complication rates (11.5% vs 11.9%; P = 0.88) between single-use and reusable endoscopes. For patients undergoing flexible ureteroscopy there were no differences in operating time (mean difference -0.05 min; P = 0.96), length of hospital stay (LOS; mean difference 0.06 days; P = 0.18) or stone-free rate (SFR; 74% vs 74.3%; P = 0.54) between the single-use and reusable flexible ureteroscope groups. CONCLUSION: This study is the largest to compare the clinical outcomes of single-use endoscopes to those of reusable endoscopes within urology, and demonstrated no difference in LOS, complication rate or SFR, with a shorter operating time associated with single-use flexible cystoscope use. It also highlights that the cost efficiency and environmental impact of single-use endoscopes is largely dependent on the caseload and reprocessing facilities available within a given institution. Urologists can therefore feel confident that whether they choose to 'use' or to 'reuse' based on the financial and environmental implications, they can do so without negatively impacting patient outcomes.

Cost Effectiveness of Systemic Treatment Intensification for Metastatic Hormone-sensitive Prostate Cancer: Is Triplet Therapy Cost Effective?

BACKGROUND AND OBJECTIVE: There has been a shift toward systemic treatment intensification for men with metastatic hormone-sensitive prostate cancer (mHSPC). Recent trials have demonstrated the efficacy of triplet therapy with an androgen receptor signalling inhibitor (ARSI), docetaxel, and androgen deprivation therapy (ADT). However, ARSI treatment is expensive. The objective was to determine the cost effectiveness of current treatments strategies for men with mHSPC. METHODS: We developed a Markov state-transition model to simulate outcomes for men with newly diagnosed mHSPC. For the simulation, patients were entered in the model in the mHSPC disease state before progressing to castration-resistant disease and finally dying from prostate cancer. Costs were calculated from a USA health sector perspective in 2022 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to account for uncertainty in the parameter estimates. We also performed scenario analyses for costs in the UK and Australian health sectors. KEY FINDINGS AND LIMITATIONS: Treatment intensification with doublet and triplet therapy resulted in an improvement in quality-adjusted survival for all strategies in comparison to ADT monotherapy. However, only docetaxel doublet therapy was cost effective at standard thresholds, with an incremental cost-effectiveness ratio of $13 647. The cost of ARSIs needed to be discounted by 47-70% before they were cost effective. Only medication costs impacted the model results. If the generic price for abiraterone acetate is used, then triplet therapy with abiraterone is the best-value option. Similar results were obtained for analyses for the UK and Australian health sectors. CONCLUSIONS AND CLINICAL IMPLICATIONS: Treatment intensification with ARSIs in men with mHSPC results in better quality-adjusted survival but is not cost effective according to standard thresholds. The costs of these medications would need to be heavily discounted before they are cost effective. The cost of generic ARSIs, once available, would render these strategies cost effective. PATIENT SUMMARY: This report examines whether increasing the number of systemic drugs used to treat a patient's metastatic hormone-sensitive prostate cancer is cost effective for the health care system. We found that the additional cost of triplet therapy does not justify the increase in patient benefit.

Social determinants of health: does socioeconomic status affect access to staging imaging for men with prostate cancer.

Socioeconomic status (SES), race and geographical factors are known to impact prostate cancer management and outcomes. We aimed to assess these factors with regard to access to novel imaging in prostate cancer. Using the Prostate Cancer Outcomes Registry of Victoria (PCOR-Vic) we identified 5256 men diagnosed with prostate cancer via biopsy. Following the introduction of government rebate, the access to MRI improved with respect to SES. Access to PET imaging remains poor with respect to SES and geographical location in the absence of Federal funding. Further improvements for men with low SES and regional areas to access PET staging.

New approaches to targeting epigenetic regulation in prostate cancer.

PURPOSE OF REVIEW: Many clinical trials are currently underway to target the epigenome of castration-resistant prostate cancer. In this review, we summarize the major epigenetic alterations that occur during prostate cancer progression, describe their biological consequences, and highlight potential of therapies that target epigenetic regulators for use in patients. RECENT FINDINGS: Epigenetic alterations frequently occur in tumour suppressor genes, DNA repair genes, and genes that regulate cell proliferation and differentiation. Unlike genetic alterations, epigenetic changes are reversible, making them promising targets for cancer therapy. Epigenetic regulators can be divided into three broad groups: writers, readers, and erasers , each with specific drug targets that are being assessed in phase I and II clinical trials for prostate cancer. CBP/p300, and BRD4 are coregulators of the androgen receptor and inhibit androgen signalling, making bromodomain extra-terminal inhibitors and CBP/p300 inhibitors attractive targets in prostate cancer. Enhancer of zeste homolog 2, a histone methyltransferase, is also a potential target in castrate-resistant prostate cancer. An emerging direction is to combine epigenetic inhibitors with other compounds to enhance their efficacy. SUMMARY: Preclinical studies indicate that the epigenome is a potential target in prostate cancer, and clinical trials are testing multiple agents that target the epigenome in different ways. However, the process of translating these therapies into the clinic is ongoing and none have yet been approved for castrate-resistant prostate cancer.

Smoking Methylation Marks for Prediction of Urothelial Cancer Risk.

BACKGROUND: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. METHODS: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC). RESULTS: The meta-analysis identified associations (P < 4.7 × 10-5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P < 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set in MCCS [N = 134; odds ratio per SD (OR) = 1.37; 95% CI, 1.00-1.90] after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (N = 440; OR = 1.09; 95% CI, 0.91-1.30). CONCLUSIONS: Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger data sets. IMPACT: DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.

A COVID-19 Test Triage Tool, Predicting Negative Results and Reducing the Testing Burden on Healthcare Systems During a Pandemic.

Background: Detecting and isolating cases of COVID-19 are amongst the key elements listed by the WHO to reduce transmission. This approach has been reported to reduce those symptomatic with COVID-19 in the population by over 90%. Testing is part of a strategy that will save lives. Testing everyone maybe ideal, but it is not practical. A risk tool based on patient demographics and clinical parameters has the potential to help identify patients most likely to test negative for SARS-CoV-2. If effective it could be used to aide clinical decision making and reduce the testing burden. Methods: At the time of this analysis, a total of 9,516 patients with symptoms suggestive of Covid-19, were assessed and tested at Mount Sinai Institutions in New York. Patient demographics, clinical parameters and test results were collected. A robust prediction pipeline was used to develop a risk tool to predict the likelihood of a positive test for Covid-19. The risk tool was analyzed in a holdout dataset from the cohort and its discriminative ability, calibration and net benefit assessed. Results: Over 48% of those tested in this cohort, had a positive result. The derived model had an AUC of 0.77, provided reliable risk prediction, and demonstrated a superior net benefit than a strategy of testing everybody. When a risk cut-off of 70% was applied, the model had a negative predictive value of 96%. Conclusion: Such a tool could be used to help aide but not replace clinical decision making and conserve vital resources needed to effectively tackle this pandemic.

What is the best way to manage ureteric calculi in the time of COVID-19? A comparison of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy (URS) in an Australian health-care setting.

Objectives: To determine the best way to intervene for ureteric stones which still require treatment during the COVID-19 pandemic, with respect to infection control. In this setting, in which resources are constrained, extracorporeal shockwave lithotripsy (SWL) has prima facie advantages over ureteroscopy (URS). It is also necessary to also consider posttreatment resource consumption in regards to complications and repeat procedures. Subjects and methods: The ideal ureteric stone treatment during a pandemic such as COVID-19 would involve minimum resource consumption and a minimum number of patient attendances. We compared all patients initially treated with SWL to those initially treated with URS for acute ureteral colic within the state of Victoria, Australia in 2017. Results: A total of 2724 ureteric stones were analyzed, a cumulative "3-month exposure and burden on the healthcare system" was calculated for each patient by their initial procedure type. The readmission rate for URS was significantly higher than for SWL, 0.92 readmissions/patient for URS versus 0.54 readmissions/patient for SWL (P < .001). The cumulative hospital stay per patient for these two procedures was 2.35 days for SWL versus 3.21 days for URS (P < .001). The number of procedures per patient was 1.52 for SWL versus 1.89 for URS (P = .0213). Conclusions: Patients with ureteric stones treated initially by SWL have shorter length of stay with fewer overall attendances and procedures at 3 months than those treated with URS. During a pandemic such as COVID-19, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS.

Which has more complications?-Shockwave lithotripsy versus endoscopic treatment of renal calculi with 1-year follow-up in an Australian population.

Introduction and objectives: Renal calculi are a common medical problem with incidence rates calculated to be approximately 6%-9% in men & 3%-4% in women worldwide. Incidence appears to be increasing. This study compares emergency presentations and unplanned readmissions between extracorporeal shock wave lithotripsy (SWL) and pyeloscopic stone treatment in the population of Victoria, Australia after 1-year follow-up. Methods: This is a population study comparing all patients with renal calculi electively treated with SWL to those initially treated with flexible ureteroscopy (URS) in Victoria, Australia. We used data linkage across the state of Victoria to follow patients treated with either modality in a 12 months period (with no urological surgery in the prior 12 months). Each patient's emergency presentations and subsequent re-admissions were followed up for 1 year after their index treatment to assess for stone complications. We assessed for selection bias between the two patient groups by comparing age, gender, insurance status, geographical location, and comorbidity scores. Results: We report stone-related complications for 739 flexible URS and 1317 SWL procedures undertaken across public and private hospitals in Victoria over 12 months. Unplanned emergency presentations within 60-days of surgery were (22/739) 2.98% for flexible URS patients and (83/1317) 6.30% for SWL patients (P = .001); however, at 12 months, this became 16.23% (120/739) for flexible URS patients and 12.83% (169/1317) for SWL patients (P = .034). Flexible URS patients were more likely than SWL patients to be admitted with 71.76% of flexible URS versus 53.97% of SWL patients requiring an admission at any given emergency presentation (P ≤ .001) within 12 months. On multivariate analysis, both flexible URS ([OR] 1.67, CI 1.23-2.26, P = .001) and being a public patient ([OR] 3.06, CI 2.24-4.18, P < .001) significantly increased the likelihood that patients required an unplanned re-admission within 12 months. Conclusions: There is work needed to reduce emergency presentations and unplanned re-admissions after both SWL and flexible URS. At 12-months follow-up, unplanned emergency visits and re-admission rates were significantly more after flexible URS. Symptoms at emergency presentation indicate that better education regarding stent management is needed, especially in the public health care system.

A Decision Aide for the Risk Stratification of GU Cancer Patients at Risk of SARS-CoV-2 Infection, COVID-19 Related Hospitalization, Intubation, and Mortality.

Treatment decisions for both early and advanced genitourinary (GU) malignancies take into account the risk of dying from the malignancy as well as the risk of death due to other causes such as other co-morbidities. COVID-19 is a new additional and immediate risk to a patient's morbidity and mortality and there is a need for an accurate assessment as to the potential impact on of this syndrome on GU cancer patients. The aim of this work was to develop a risk tool to identify GU cancer patients at risk of diagnosis, hospitalization, intubation, and mortality from COVID-19. A retrospective case showed a series of GU cancer patients screened for COVID-19 across the Mount Sinai Health System (MSHS). Four hundred eighty-four had a GU malignancy and 149 tested positive for SARS-CoV-2. Demographic and clinical variables of >38,000 patients were available in the institutional database and were utilized to develop decision aides to predict a positive SARS-CoV-2 test, as well as COVID-19-related hospitalization, intubation, and death. A risk tool was developed using a combination of machine learning methods and utilized BMI, temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation. The risk tool for predicting a diagnosis of SARS-CoV-2 had an AUC of 0.83, predicting hospitalization for management of COVID-19 had an AUC of 0.95, predicting patients requiring intubation had an AUC of 0.97, and for predicting COVID-19-related death, the risk tool had an AUC of 0.79. The models had an acceptable calibration and provided a superior net benefit over other common strategies across the entire range of threshold probabilities.

Pressurized-Bag Irrigation Versus Hand-Operated Irrigation Pumps During Ureteroscopic Laser Lithotripsy: Comparison of Infectious Complications.

Introduction and Objectives: A variety of irrigation systems are available during ureteroscopy. We sought to compare gravity-driven pressure bags with hand-operated irrigation pumps in terms of postoperative complications after ureteroscopy with lithotripsy. Methods: A retrospective analysis of 234 patients undergoing flexible ureteropyeloscopy with laser lithotripsy by 24 supervised trainees over 4 years at a single teaching institution. Patients were divided into those who had procedures performed by using gravity-driven pressure bags fixed at 60 to 204 cm H2O, vs those who had procedures performed by using a hand-operated irrigation pump capable of delivering 1 to 10 mL per flush. Variables including surgical duration, hypotension, fever, sepsis, and hematuria were extracted from the charts, along with the surgical techniques utilized. Statistical analyses included chi-squared tests and Student's t-tests. Results: There were no differences in gender, age, indication, or stone size in the two groups. Postoperative systemic inflammatory response syndrome was significantly greater in the hand-assisted n = 11/144 (7.6%) compared with the fixed irrigation group n = 1/90 (1.1%); p = 0.032. Emergency room presentations were greater in the hand irrigation group, n = 46/144 (32%) vs n = 12/90 (13%) in the pressure-bag irrigation, p = 0.002. Postoperative fever was also greater in the hand pump irrigation cohort compared with the continuous pressure cohort (13/144 [9%] vs 1/90 [1%], p = 0.011). No statistical difference was found between the two groups with respect to stone clearance and subsequent procedures required (p = 0.123). Conclusions: This analysis suggests that using continuous flow irrigation at a fixed maximum pressure of 150 mmHg (204 cm H2O) or less may result in decreased pain, infection, and sepsis compared with handheld pressure irrigation.

The Protective Effect of Zinc Against Liver Ischaemia Reperfusion Injury in a Rat Model of Global Ischaemia.

BACKGROUND: Ischaemia-reperfusion injury (IRI) is a major obstacle during liver transplantation and resection surgeries for cancer, with a need for effective and safe drugs to reduce IRI. Zinc preconditioning has been shown to protect against liver IRI in a partial (70%) ischaemia model. However, its efficacy against a clinically relevant Pringle manoeuvre that results in global liver ischaemia (100%) is unknown. AIMS: The aim of this study was to test the efficacy of zinc preconditioning in a rat model of global liver ischaemia. METHODS: Rats were preconditioned via subcutaneous injection of 10 mg/kg of ZnCl2, 24 h and 4 h before ischaemia. Total liver ischaemia (100%) was induced by placing a clamp across the portal triad for 30 min. Liver injury was assessed by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels in blood taken before ischaemia (baseline) and at 1, 2, 4, 24, 48, 72, 96 and 120 hours after ischaemia. Animals were culled after 7 days, and the harvested livers were histologically analysed. RESULTS: On a two-way repeated-measures analysis of variance, there was a statistically significant (p = 0.025) difference in the mean ALT levels between saline- and ZnCl2-treated groups. Specifically at 24 h after ischaemia, the ALT (341 ± 99 U/L) and AST (606 ± 78 U/L) in the zinc-treated group were significantly less than the ALT (2863 ± 828 U/L) and AST (3591 ± 948 U/L) values in the saline-treated group. Zinc significantly reduced neutrophil infiltration and necrosis compared with the saline control. CONCLUSION: Zinc preconditioning reduces the overall hepatocellular damage from IRI. These results lay the foundation to assess the benefit of zinc preconditioning for clinical applications.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

A Cost-effectiveness Analysis of Systemic Therapy for Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: Following the recent publication of results from randomized trials that have demonstrated a survival benefit for the addition of docetaxel or abiraterone acetate to androgen deprivation therapy (ADT) in the treatment of metastatic prostate cancer, it is important to assess whether the benefits of treatment with these agents outweigh their costs. OBJECTIVE: To perform a cost-effectiveness analysis of immediate docetaxel or abiraterone acetate treatment in addition to ADT in men with metastatic hormone-sensitive prostate cancer (PC). DESIGN, SETTING, AND PARTICIPANTS: We developed a state-transition model to simulate the natural progression of metastatic PC. Model parameters were derived from the published literature and through calibration to observed epidemiological data. Following diagnosis, a hypothetical cohort of men with metastatic hormone-sensitive PC could be treated with docetaxel+ADT, abiraterone+ADT, or ADT alone. Once disease progresses to castration-resistant PC, treatment with one of the approved therapies in this setting was initiated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were quality-adjusted life years (QALYs) and costs from a US private payer, health sector perspective. RESULTS AND LIMITATIONS: Compared to treatment with ADT alone, docetaxel and abiraterone resulted in a discounted quality-adjusted survival gain of 3.6 and 22.0mo, respectively. Using standard cost-effectiveness metrics, treatment with docetaxel and ADT provides high value for money (ie, is cost effective) with an incremental cost-effectiveness ratio (ICER) of $34723, compared to an ICER of $295212 for abiraterone. The monthly cost of abiraterone would have to be less than $3114 for it to be cost effective. CONCLUSIONS: Docetaxel+ADT is likely the most cost-effective treatment option for men with metastatic hormone-sensitive PC. Although potentially more effective than docetaxel, the costs of abiraterone would have to be considerably lower to match the cost effectiveness of docetaxel+ADT. PATIENT SUMMARY: This study evaluated the balance of costs and benefits for treatment of metastatic hormone-sensitive prostate cancer with docetaxel plus androgen deprivation therapy (ADT), abiraterone plus ADT, or ADT alone. We found that treatment with docetaxel plus ADT likely represents the most cost-effective option in this setting.

Why is it worth testing the ability of zinc to protect against ischaemia reperfusion injury for human application.

Ischaemia (interruption in the blood/oxygen supply) and subsequent damage induced by reperfusion (restoration of blood/oxygen supply) ultimately leads to cell death, tissue injury and permanent organ dysfunction. The impact of ischaemia reperfusion injury (IRI) is not limited to heart attack and stroke but can be extended to patients undergoing surgeries such as partial nephrectomy for renal cancer, liver resection for colorectal cancer liver metastasis, cardiopulmonary bypass, and organ transplantation. Unfortunately, there are no drugs that can protect organs against the inevitable peril of IRI. Recent data show that a protocol incorporating specific Zn formulation, dosage, number of dosages, time of injection, and mode of Zn delivery (intravenous) and testing of efficacy in a large preclinical sheep model of IRI strongly supports human trials of Zn preconditioning. No doubt, scepticism still exists among funding bodies and research fraternity on whether Zn, a naturally occurring metal, will work where everything else has failed. Therefore, in this article, we review the conflicting evidence on the promoter and protector role of Zn in the case of IRI and highlight factors that may help explain the contradictory evidence. Finally, we review the literature related to the knowledge of Zn's mechanism of action on ROS generation, apoptosis, HIF activation, inflammation, and signal transduction pathways, which highlight Zn's likelihood of success compared to various other interventions targeting IRI.

Tumor size and postoperative kidney function following radical nephrectomy.

Background: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors. Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function. Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function. Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients. Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.

Incident Chronic Kidney Disease After Radical Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: Chronic kidney disease (CKD) after surgery for kidney cancer is common, and is associated with increased morbidity and mortality. This study aimed to identify factors associated with incident CKD in patients managed with radical nephrectomy. PATIENTS AND METHODS: All patients diagnosed with renal cell carcinoma between January 2012 and December 2013 were ascertained from state-based cancer registries in Queensland and Victoria. Information on patient, tumor, and health service characteristics was obtained via chart review. Multivariable logistic regression was used to evaluate exposures associated with incident CKD (estimated glomerular filtration rate [eGFR] <60 mL per minute per 1.73 m2) at 12 months after nephrectomy. RESULTS: Older age (adjusted odds ratio [aOR] per 5-year increase, 1.5; 95% confidence interval [CI], 1.4-1.6), male sex (aOR, 1.4; 95% CI, 1.0-2.0), obese compared with not obese (aOR, 1.8; 95% CI, 1.2-2.7), rural compared with urban place of residence (aOR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of incident CKD. Lower preoperative eGFR was also associated with a higher risk of incident CKD. Management in private compared with public hospitals was also associated with a higher risk of CKD (aOR, 1.6; 95% CI, 1.2-2.2). Factors related to tumor size and cancer severity were also associated with worse postoperative kidney function, although it is likely this was a consequence of selection bias. CONCLUSION: Patient characteristics have the strongest associations with incident CKD after radical nephrectomy. Potential risk factors were reasonably similar to recognized CKD risk factors for the general population. Patients who undergo nephrectomy who have CKD risk factors might benefit from ongoing postoperative screening for deterioration of kidney function.

Erectile dysfunction: a global review of intracavernosal injectables.

PURPOSE: Data assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice. METHODS: A systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents. RESULTS: ICIs demonstrate clinical efficacy in 54-100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3-6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved. CONCLUSIONS: ICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.

Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic.

Acute kidney injury (AKI) as a result of ischaemia-reperfusion represents a major healthcare burden worldwide. Mortality rates from AKI in hospitalized patients are extremely high and have changed little despite decades of research and medical advances. In 1986, Murry et al. demonstrated for the first time the phenomenon of ischaemic preconditioning to protect against ischaemia-reperfusion injury (IRI). This seminal finding paved the way for a broad body of research, which attempted to understand and ultimately harness this phenomenon for human application. The ability of preconditioning to limit renal IRI has now been demonstrated in multiple different animal models. However, more than 30 years later, a safe and consistent method of protecting human organs, including the kidneys, against IRI is still not available. This review highlights agents which, despite strong preclinical data, have recently failed to reduce AKI in human trials. The multiple reasons which may have contributed to the failure to translate some of the promising findings to clinical therapies are discussed. Agents which hold promise in the clinic because of their recent efficacy in preclinical large animal models are also reviewed.