Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.

Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real-time polymerase chain reaction assay. Our systematic analysis of androgen deprivation-associated genes involved multiple biological processes, including neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma-aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene-disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type-1 angiotensin II receptor, brain-derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5-hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT-mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

Antibiotic Use in Hospital Urinary Tract Infections After FDA Regulation.

BACKGROUND: The FDA issued a "black box" warning regarding risks of fluoroquinolones in 2008 with updates in 2011, 2013, and 2016. OBJECTIVE: To examine antimicrobial use in hospital-treated UTIs from 2000 to 2020. DESIGN: Cross-sectional study with interrupted time series analysis. PARTICIPANTS: Patient encounters with a diagnosis of UTI from January 2000 to March 2020, excluding diagnoses of renal abscess, chronic cystitis, and infection of the gastrointestinal tract, lungs, or prostate. MAIN MEASURES: Monthly use of fluoroquinolone and non-fluoroquinolone antibiotics were assessed. Fluoroquinolone resistance was assessed in available cultures. Interrupted time series analysis examined level and trend changes of antimicrobial use with each FDA label change. KEY RESULTS: A total of 9,950,790 patient encounters were included. From July 2008 to March 2020, fluoroquinolone use declined from 61.7% to 11.7%, with similar negative trends observed in inpatients and outpatients, age ≥ 60 and < 60 years, males and females, patients with and without pyelonephritis, and across physician specialties. Ceftriaxone use increased from 26.4% encounters in July 2008 to 63.6% of encounters in March 2020. Among encounters with available culture data, fluoroquinolone resistance declined by 28.9% from 2009 to 2020. On interrupted time series analysis, the July 2008 FDA warning was associated with a trend change (-0.32%, < 0.001) and level change (-5.02%, p < 0.001) in monthly fluoroquinolone use. CONCLUSIONS: During this era of "black box" warnings, there was a decline in fluoroquinolone use for hospital-treated UTI with a concomitant decline in fluoroquinolone resistance and rise in ceftriaxone use. Efforts to restrict use of a medication class may lead to compensatory increases in use of a single alternative agent with changes in antimicrobial resistance profiles.

Methodological rigour in preclinical urology: a systematic review reporting research quality over a 14-year period.

OBJECTIVE: To investigate the prevalence and trends of essential study design elements in preclinical urological studies, as well as key factors that may improve methodological rigour, as the demand for methodological rigour in preclinical studies is increasing since research reproducibility and transparency in the medico-scientific field are being questioned. METHODS AND RESULTS: PubMed was searched to include preclinical urological studies published between July 2007 to June 2021. A total of 3768 articles met the inclusion criteria. Data on study design elements and animal models used were collected. Citation density was also examined as a surrogate marker of study influence. We performed an analysis of the prevalence of seven critical study design elements and temporal patterns over 14 years. Randomisation was reported in 50.0%, blinding in 15.0%, sample size estimation in 1.0%, inclusion of both sexes in 6.3%, statistical analysis in 97.1%, housing and husbandry in 47.7%, and inclusion/exclusion criteria in 5.0%. Temporal analysis showed that the implementation of these study design elements has increased, except for inclusion of both sexes and inclusion/exclusion criteria. Reporting study design elements were associated with increased citation density in randomisation and statistical analysis. CONCLUSIONS: The risk of bias is prevalent in 14-year publications describing preclinical urological research, and the quality of methodological rigour is barely related to the citation density of the article. Yet five study design elements (randomisation, blinding, sample size estimation, statistical analysis, and housing and husbandry) proposed by both the National Institutes of Health and Animal Research: Reporting of In Vivo Experiments guidelines have been either well reported or are being well reported over time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022233125.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Evaluation of a photodynamic therapy agent using a canine prostate cancer model.

BACKGROUND: Male dogs can develop spontaneous prostate cancer, which is similar physiologically to human disease. Recently, Tweedle and coworkers have developed an orthotopic canine prostate model allowing implanted tumors and therapeutic agents to be tested in a more translational large animal model. We used the canine model to evaluate prostate-specific membrane antigen (PSMA)-targeted gold nanoparticles as a theranostic approach for fluorescence (FL) imaging and photodynamic therapy (PDT) of early stage prostate cancer. METHODS: Dogs (four in total) were immunosuppressed with a cyclosporine-based immunosuppressant regimen and their prostate glands were injected with Ace-1-hPSMA cells using transabdominal ultrasound (US) guidance. Intraprostatic tumors grew in 4-5 weeks and were monitored by ultrasound (US). When tumors reached an appropriate size, dogs were injected intravenously (iv) with PSMA-targeted nano agents (AuNPs-Pc158) and underwent surgery 24 h later to expose the prostate tumors for FL imaging and PDT. Ex vivo FL imaging and histopathological studies were performed to confirm PDT efficacy. RESULTS: All dogs had tumor growth in the prostate gland as revealed by US. Twenty-four hours after injection of PSMA-targeted nano agents (AuNPs-Pc158), the tumors were imaged using a Curadel FL imaging device. While normal prostate tissue had minimal fluorescent signal, the prostate tumors had significantly increased FL. PDT was activated by irradiating specific fluorescent tumor areas with laser light (672 nm). PDT bleached the FL signal, while fluorescent signals from the other unexposed tumor tissues were unaffected. Histological analysis of tumors and adjacent prostate revealed that PDT damaged the irradiated areas to a depth of 1-2 mms with the presence of necrosis, hemorrhage, secondary inflammation, and occasional focal thrombosis. The nonirradiated areas showed no visible damages by PDT. CONCLUSION: We have successfully established a PSMA-expressing canine orthotopic prostate tumor model and used the model to evaluate the PSMA-targeted nano agents (AuNPs-Pc158) in the application of FL imaging and PDT. It was demonstrated that the nano agents allowed visualization of the cancer cells and enabled their destruction when they were irradiated with a specific wavelength of light.

Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Cost-effectiveness analysis of arterial catheter insertion on robotic-assisted laparoscopic prostatectomy.

INTRODUCTION: To evaluate the utility, outcomes, and cost of arterial line placement in a single institution cohort of patients undergoing robotic-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: A retrospective chart review was performed at a large tertiary care center from July 2018 through January 2021. Hospital costs and cost-effective analysis was performed on patients with and without arterial line placement. Means with standard deviations were used to report continuous variables, while numbers and percentages were utilized to describe categorical variables. T-tests and Chi-square tests compared categorical and continuous variables across study cohorts, respectively. Multivariable analyses were used to examine the association between A-line placement and outcomes as mentioned above adjusting for the effect of other co-variables. RESULTS: Among the 296 included patients, 138 (46.6%) had arterial lines. No preoperative patient characteristic predicted arterial line placement. Rates of complications and re-admissions were not statistically significant between the two groups. Arterial line use was associated with higher volumes of intraoperative fluid administration, as well as a longer hospital length of stay. Total cost and operative time did not significantly differ between cohorts, but arterial line placement increased variability of these factors. CONCLUSION: The use of arterial lines in patients undergoing RALP is not necessarily guideline-driven and does not decrease the rate of perioperative complications. However, it is associated with longer length of stay and increases variability in charge. These data show that the surgical team and anesthesia team should critically evaluate the need for arterial line placement in patients undergoing RALP.

5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Increased cytokine gene expression and cognition risk associated with androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. METHODS: Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge database. RESULTS: A total of 1952 DEGs in the Alzheimer patient cohort and 101 DEGs were identified in ADT treated prostate cancer patients. Comparing both data sets provided a subset of 33 commonly expressed genes involving cytokine-cytokine signaling with an over representation of cytokine-cytokine receptor interaction, inflammatory cytokines, signaling by interleukins together with alterations in the circulating lymphocyte repertoire, adaptive immune responses, regulation of cytokine production, and changes in T-cell subsets. Additionally, lipopolysaccharide, tumor necrosis factor, and toll-like receptors were identified as upstream transcriptional regulators of these pathways. The most commonly expressed genes viz. IL-17A, CCL2, IL-10, IL-6, IL-1RN, LIF/LIFR were further validated by quantitative RT-PCR exhibited higher expression in antiandrogen treated neuronal, glial, and androgen-responsive prostate cancer cells, compared to no-androgen antagonist treatment. CONCLUSIONS: Our findings suggest that changes in cytokine signaling under the influence of ADT in prostate cancer patients may be linked with cognitive impairment presenting new avenues for diagnostic and therapeutic development in combating brain deficits.

Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.

Clinically Significant Prostate Cancer Detection After a Negative Prebiopsy MRI Examination: Comparison of Biparametric Versus Multiparametric MRI.

BACKGROUND. The frequency of clinically significant prostate cancer (csPCa) following negative biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) has not been well investigated in direct comparative studies. OBJECTIVE. The purposes of this study were to compare the frequency of csPCa after negative prebiopsy bpMRI and mpMRI and to evaluate factors predictive of csPCa in the two cohorts. METHODS. This retrospective study included 232 men (mean age, 64.5 years) with negative bpMRI from August 2017 to March 2020 and 193 men (mean age, 69.0 years) with negative mpMRI from January 2018 to December 2018. PI-RADS category 1 or 2 was defined as negative. The study institution offered bpMRI as a low-cost self-pay option for patients without insurer coverage of prebiospy mpMRI. Patient characteristics and subsequent biopsy results were recorded. CsPCa was defined as Gleason score of 3 + 4 or greater. Multivariable regression analyses were performed to identify independent predictors of csPCa. The AUC of PSA density (PSAD) for csPCA was computed, and the diagnostic performance of PSAD was assessed at a clinically established threshold of 0.15 ng/mL2. RESULTS. Systematic biopsy was performed after negative bpMRI for 41.4% (96/232) of patients and after negative mpMRI for 30.5% (59/193) (p = .02). Among those undergoing biopsy, csPCa was present in 15.6% (15/96) in the bpMRI cohort versus 13.6% (8/59) in the mpMRI cohort (p = .69). The NPV for csPCa was 84% (81/96) for bpMRI and 86% (51/59) for mpMRI. In multivariable analyses, independent predictors of csPCa included smaller prostate volume (OR, 0.27; p < .001) and greater PSAD (OR, 3.09; p < .001). In multivariable models, bpMRI (compared with mpMRI) was not independently predictive of csPCa (p > .05). PSAD had an AUC for csPCa of 0.71 (95% CI, 0.56-0.87) in the bpMRI cohort versus 0.68 (95% CI, 0.42-0.93) in the mpMRI cohort. For detecting csPCa, a PSAD threshold of 0.15 ng/mL2 had NPV of 90% and PPV of 28%, in the bpMRI cohort versus NPV of 92% and PPV of 44% in the mpMRI cohort. CONCLUSION. The frequencies of csPCa were not significantly different at systematic biopsy performed after negative bpMRI and mpMRI examinations. PSAD had similar diagnostic utility for csPCa in the two cohorts. CLINICAL IMPACT. Either bpMRI or mpMRI, in combination with PSAD measurement, can help avoid negative prostate biopsies.

Risk factors for postoperative Clostridium difficile infection after radical cystectomy for bladder cancer: a NSQIP database analysis.

INTRODUCTION: Patients undergoing cystectomy for bladder cancer are at an increased risk for Clostridium difficile infection (CDI) due to prolonged antibiotics and underlying comorbidities. We aim to evaluate CDI risk factors in cystectomy patients. MATERIALS AND METHODS: Utilizing National Surgical Quality Improvement Program (NSQIP), patients undergoing cystectomy with diagnosis of bladder cancer between 2015-2017 were included. Baseline demographics including age, sex, comorbidities, and preoperative labs were collected. Univariate and multivariable logistic regression were used to evaluate risk factors for and complications of CDI during the index hospitalization. RESULTS: There were a total of 6,432 patients included in the analysis, with 6,242 (96%) and 190 (4%) in the non-CDI vs. CDI groups, respectively. Patients with a diagnosis of postoperative CDI were more likely to be female [4.09% vs. 2.71%, p = 0.001] and have lower preoperative albumin [3.78 g/dL (0.52) vs. 3.92 g/dL (0.48), p = 0.003]. Patients with a history of female sex (OR 1.46, p = 0.03), neobladder (OR 1.57, p = 0.01), and low preoperative albumin (OR 1.45, p = 0.04) were at the highest risk for development of CDI postoperatively. Patients with a diagnosis of CDI were more likely to experience readmission within 30 days (31.1% vs. 19.2%, p < 0.001). CONCLUSION: Utilizing the NSQIP database, we identified predictors for development of CDI in cystectomy patients. Female sex, continent diversion, and low preoperative albumin all significantly increased the rate of CDI. While our findings are retrospective, they are compelling enough to warrant further prospective investigation.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

PURPOSE: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. MATERIALS AND METHODS: We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. RESULTS: Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). CONCLUSIONS: In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

T1 and T2 MR fingerprinting measurements of prostate cancer and prostatitis correlate with deep learning-derived estimates of epithelium, lumen, and stromal composition on corresponding whole mount histopathology.

OBJECTIVES: To explore the associations between T1 and T2 magnetic resonance fingerprinting (MRF) measurements and corresponding tissue compartment ratios (TCRs) on whole mount histopathology of prostate cancer (PCa) and prostatitis. MATERIALS AND METHODS: A retrospective, IRB-approved, HIPAA-compliant cohort consisting of 14 PCa patients who underwent 3 T multiparametric MRI along with T1 and T2 MRF maps prior to radical prostatectomy was used. Correspondences between whole mount specimens and MRI and MRF were manually established. Prostatitis, PCa, and normal peripheral zone (PZ) regions of interest (ROIs) on pathology were segmented for TCRs of epithelium, lumen, and stroma using two U-net deep learning models. Corresponding ROIs were mapped to T2-weighted MRI (T2w), apparent diffusion coefficient (ADC), and T1 and T2 MRF maps. Their correlations with TCRs were computed using Pearson's correlation coefficient (R). Statistically significant differences in means were assessed using one-way ANOVA. RESULTS: Statistically significant differences (p < 0.01) in means of TCRs and T1 and T2 MRF were observed between PCa, prostatitis, and normal PZ. A negative correlation was observed between T1 and T2 MRF and epithelium (R = - 0.38, - 0.44, p < 0.05) of PCa. T1 MRF was correlated in opposite directions with stroma of PCa and prostatitis (R = 0.35, - 0.44, p < 0.05). T2 MRF was positively correlated with lumen of PCa and prostatitis (R = 0.57, 0.46, p < 0.01). Mean T2 MRF showed significant differences (p < 0.01) between PCa and prostatitis across both transition zone (TZ) and PZ, while mean T1 MRF was significant (p = 0.02) in TZ. CONCLUSION: Significant associations between MRF (T1 in the TZ and T2 in the PZ) and tissue compartments on corresponding histopathology were observed. KEY POINTS: • Mean T2 MRF measurements and ADC within cancerous regions of interest dropped with increasing ISUP prognostic groups (IPG). • Mean T1 and T2 MRF measurements were significantly different (p < 0.001) across IPGs, prostatitis, and normal peripheral zone (NPZ). • T2 MRF showed stronger correlations in the peripheral zone, while T1 MRF showed stronger correlations in the transition zone with histopathology for prostate cancer.

Systematic Review of the Management of Ureteroarterial Fistulas After Ileal Conduit Urinary Diversion.

OBJECTIVE. No studies or guidelines exist to direct management of ureteroarterial fistula (UAF) after ileal conduit urinary diversion in which the possible risks and complications associated with stent-graft infection from the conduit flora must be reconciled with those of open surgical repair. This study seeks to characterize the clinical presentation, pathogenesis, and optimal diagnostic and therapeutic management of this entity through a systematic review of the literature. MATERIALS AND METHODS. A systematic search of the English-language literature using the PubMed, Scopus, and ScienceDirect databases was performed: 264 abstracts were identified. From those abstracts, 32 studies comprising 40 patients with 43 UAFs were selected for analysis. Data points including demographics, clinical presentation, UAF specifications, procedural details, postprocedural complications, and clinical outcomes were reviewed. RESULTS. Predisposing factors included female sex, chronic ureteral stent placement, and past surgical intervention and irradiation for pelvic malignancy. Fistulization was overwhelmingly unilateral (95.0% of patients) and included the common iliac artery (90.7% of UAFs). Combined endovascular and endoureteral modalities presented similar outcomes compared with surgical approaches in terms of UAF-related mortality (7.1% vs 13.3%, respectively) and complication rates (28.6% vs 26.7%) during a similar median follow-up period (9.5 vs 14.0 months). Endovascular stent-graft infections were present in 14.3% of cases and represented a leading indication for reintervention after endovascular management (50.0%). CONCLUSION. Short- and intermediate-term outcomes of combined endovascular and endoureteral techniques compare favorably with those of surgical approaches in the treatment of UAF after ileal conduit urinary diversion. Although there is a relatively low stent-graft infection rate, close follow-up within the first year after the procedure is required given the propensity of complications to develop during this window. The use of postprocedural antibiotics is uncertain but is likely prudent.

Diagnostic Yield of Incremental Biopsy Cores and Second Lesion Sampling for In-Gantry MRI-Guided Prostate Biopsy.

BACKGROUND. In-gantry MRI-guided biopsy (MRGB) of the prostate has been shown to be more accurate than other targeted prostate biopsy methods. However, the optimal number of cores to obtain during in-gantry MRGB remains undetermined. OBJECTIVE. The purpose of this study was to assess the diagnostic yield of obtaining an incremental number of cores from the primary lesion and of second lesion sampling during in-gantry MRGB of the prostate. METHODS. This retrospective study included 128 men with 163 prostate lesions who underwent in-gantry MRGB between 2016 and 2019. The men had a total of 163 lesions sampled with two or more cores, 121 lesions sampled with three or more cores, and 52 lesions sampled with four or more cores. A total of 40 men underwent sampling of a second lesion. Upgrade on a given core was defined as a greater International Society of Urological Pathology (ISUP) grade group (GG) relative to the previously obtained cores. Clinically significant prostate cancer (csPCa) was defined as ISUP GG 2 or greater. RESULTS. The frequency of any upgrade was 12.9% (21/163) on core 2 versus 10.7% (13/121) on core 3 (p = .29 relative to core 2) and 1.9% (1/52) on core 4 (p = .03 relative to core 3). The frequency of upgrade to csPCa was 7.4% (12/163) on core 2 versus 4.1% (5/121) on core 3 (p = .13 relative to core 2) and 0% (0/52) on core 4 (p = .07 relative to core 3). The frequency of upgrade on core 2 was higher for anterior lesions (p < .001) and lesions with a higher PI-RADS score (p = .007); the frequency of upgrade on core 3 was higher for apical lesions (p = .01) and lesions with a higher PI-RADS score (p = .01). Sampling of a second lesion resulted in an upgrade in a single patient (2.5%; 1/40); both lesions were PI-RADS category 4 and showed csPCa. CONCLUSION. When performing in-gantry MRGB of the prostate, obtaining three cores from the primary lesion is warranted to optimize csPCa diagnosis. Obtaining a fourth core from the primary lesion or sampling a second lesion has very low yield in upgrading cancer diagnoses. CLINICAL IMPACT. To reduce patient discomfort and procedure times, operators may refrain from obtaining more than three cores or second lesion sampling.

Possible Bioenergetic Biomarker for Chronic Cancer-Related Fatigue.

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent, debilitating, and persistent symptom experienced by patients receiving cancer treatments. Up to 71% of men with prostate cancer receiving radiation therapy experience acute and persistent CRF. There is neither an effective therapy nor a diagnostic biomarker for CRF. This pilot study aimed to discover potential biomarkers associated with chronic CRF in men with prostate cancer receiving radiation therapy. METHODS: We used a longitudinal repeated-measures research design. Twenty men with prostate cancer undergoing radiation therapy completed all study visits. CRF was evaluated by a well-established and validated questionnaire, the Patient-Reported Outcomes Measurement Information System for Fatigue (PROMIS-F) Short Form. In addition, peripheral blood mononuclear cells were harvested to quantify ribonucleic acid (RNA) gene expression of mitochondria-related genes. Data were collected before, during, on completion, and 24 months postradiation therapy and analyzed using paired t-tests and repeated-measures analysis of variance. RESULTS: The mean of the PROMIS-F T score was significantly increased over time in patients with prostate cancer, remaining elevated at 24 months postradiation therapy compared to baseline. A significant downregulated BC1 ubiquinol-cytochrome c reductase synthesis-like (BCS1L) was observed over time during radiation therapy and at 24 months postradiation therapy. An increased PROMIS-F score was trended with downregulated BCS1L in patients 24 months after completing radiation therapy. DISCUSSION: This is the first evidence to describe altered messenger RNA for BCS1L in chronic CRF using the PROMIS-F measure with men receiving radiation therapy for prostate cancer. CONCLUSION: Our results suggest that peripheral blood mononuclear cell messenger RNA for BCS1L is a potential biomarker and therapeutic target for radiation therapy-induced chronic CRF in this clinical population.

NCCN Guidelines Insights: Kidney Cancer, Version 1.2021.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.

Psychosocial mechanisms of a behavioral treatment for urinary incontinence of prostate cancer survivors.

Purpose: We examined underlying psychosocial processes of a behavioral treatment for urinary incontinence (UI) of prostate cancer survivors.Design: Secondary analysis of data collected from a clinical trial.Sample: Two hundred forty-four prostate cancer survivors who participated in a clinical trial of behavioral intervention to UI as intervention or control subjects.Methods: The participants had a 3-month behavioral intervention or usual care and were followed up for an additional 3 months. They were assessed at baseline, 3, and 6 months. Latent growth curve models were performed to examine trajectories of each study variable and relationships among the variables.Findings: Increasing self-efficacy and social support were significantly and independently associated with more reduction of urinary leakage frequency over time.Implications for psychosocial oncology: Providing problem-solving skills and social support, including peer support, are essential for empowering patients to reduce UI.