To conduct a prospective study to examine whether there are pretreatment and post-treatment disparities in urinary, sexual, and bowel quality of life (QOL) by race or ethnicity, education, or income ...in men with clinically localized prostate cancer (PCa.)
Participants (N = 1508; 81% white; 12% black; 7% Hispanic; 50% surgery; 27% radiotherapy; 23% active surveillance) completed the Expanded Prostate Cancer Index Composite measure of PCa-specific QOL prior to treatment, 6 weeks, 6, 12, 18, and 24 months after treatment. We analyzed pretreatment differences in QOL with multivariable linear regression and post-treatment differences with generalized estimating equation models.
Blacks and Hispanics (compared with whites) and men with lower income had worse pretreatment urinary function; poorer and less educated men had worse pretreatment sexual function (P < .05). In adjusted models, among men treated surgically, blacks and Hispanics had worse bowel function compared with whites, and men with lower income experienced more sexual bother and slower recovery in urinary function. Not all racial or ethnic differences favored whites; blacks had higher sexual function than whites prior to surgery and improved faster after surgery. Blacks receiving radiotherapy had lower post-treatment bowel bother than whites (P < .05).
Controlling for baseline QOL, there were some post-treatment disparities in urinary and sexual QOL that suggest the need to investigate whether treatment quality and access to follow-up care is equitable. However, survivorship disparities may, to a greater extent, reflect disadvantages in baseline health that exacerbate QOL issues after treatment.
Multiple scoring systems have been proposed for prostate MRI reporting. We sought to review the clinical impact of the new Prostate Imaging Reporting and Data System v2 (PI-RADS) and compare those ...results to our proposed Simplified Qualitative System (SQS) score with respect to detection of prostate cancers and clinically significant prostate cancers.
All patients who underwent multiparametric prostate MRI (mpMRI) had their images interpreted using PI-RADS v1 and SQS score. PI-RADS v2 was calculated from prospectively collected data points. Patients with positive mpMRIs were then referred by their urologists for enrollment in an IRB-approved prospective phase III trial of mpMRI-Ultrasound (MR/TRUS) fusion biopsy of suspicious lesions. Standard 12-core biopsy was performed at the same setting. Clinical data were collected prospectively.
1060 patients were imaged using mpMRI at our institution during the study period. 341 participants were then referred to the trial. 312 participants underwent MR/TRUS fusion biopsy of 452 lesions and were included in the analysis. 202 participants had biopsy-proven cancer (64.7%) and 206 (45.6%) lesions were positive for cancer. Distribution of cancer detected at each score produced a Gaussian distribution for SQS while PI-RADS demonstrates a negatively skewed curve with 82.1% of cases being scored as a 4 or 5. Patient-level data demonstrated AUC of 0.702 (95% CI 0.65 to 0.73) for PI-RADS and 0.762 (95% CI 0.72 to 0.81) for SQS (p< 0.0001) with respect to the detection of prostate cancer. The analysis for clinically significant prostate cancer at a per lesion level resulted in an AUC of 0.725 (95% CI 0.69 to 0.76) and 0.829 (95% CI 0.79 to 0.87) for the PI-RADS and SQS score, respectively (p< 0.0001).
mpMRI is a useful tool in the workup of patients at risk for prostate cancer, and serves as a platform to guide further evaluation with MR/TRUS fusion biopsy. SQS score provided a more normal distribution of scores and yielded a higher AUC than PI-RADS v2. However until our findings are validated, we recommend reporting of detailed sequence-specific findings. This will allow for prospectively collected data to be utilized in determining the impact of ongoing changes to these scoring systems as our understanding of mpMRI interpretation evolves.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To assess functional outcomes and complications of ureteroneocystotomies (UNCs) with or without psoas hitch or Boari flap in the reconstruction and repair of the ureter. Methods We reviewed ...a consecutive series of patients that underwent open ureteral reconstruction for ureteral obstruction or injury. Underlying ureteral disorder, preoperative and postoperative estimated glomerular filtration rate (eGFR), and imaging studies regarding resolution of hydronephrosis were assessed. Results A total of 100 ureteral reimplantations performed at our institution from November 1986 to August 2012 were identified: 24 primary ureteroneocystotomies, 58 with psoas hitch, and 18 with Boari flap. Median follow-up was 48.7 months (range 12.3-253 months). The most common underlying disorder was ureteral transitional cell cancer (TCC). Men were found to have more frequent underlying chronic ureteral disorders with chronic renal failure when compared to women. Ureteral stents were placed in 81% and were removed after a median of 33 days (range 2-161 days). Resolution of hydronephrosis was noted in 81% of the patients. The eGFR deteriorated significantly over time only in male patients ( P = .001). Postoperative complications included stent-related dysuria, urinary tract infection, and contrast-extravasation on cystogram necessitating prolonged urethral and ureteral catheter drainage. Conclusion Excellent functional outcome without significant morbidity associated with ureteral reimplantation/reconstruction was achieved. Despite resolution of hydronephrosis in the vast majority of patients, those with chronic underlying ureteral disorder and renal failure did not show improvement of their eGFR.
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major ...effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract The driving force behind oncoproteomics is to identify biomarker signatures associated with a particular malignancy. Here, we have for the first time used large-scale recombinant scFv ...antibody microarrays in an attempt to classify metastatic breast cancer versus healthy controls, based on differential protein expression profiling of whole serum samples. Using this multiplexed and miniaturised assay set-up providing pM range sensitivities, breast cancer could be classified with a specificity and sensitivity of 85% based on 129 serum analytes. However, by adopting a condensed 11 analyte biomarker signature, composed of nine non-redundant serum proteins, we were able to distinguish cancer versus healthy serum proteomes with a 95% sensitivity and specificity, respectively. When a subgroup of patients, not receiving anti-inflammatory drugs, was analysed, a novel eight analyte biomarker signature with a further improved predictive power was indicated. In a longer perspective, antibody microarray analysis could provide a tool for the development of improved diagnostics and intensified biomarker discovery for breast cancer patients.
Abstract A renewed global interest in manned space-exploration has emerged, propelled by the challenge of reaching a new frontier: travel to the Red Planet, Mars. As the physiologic changes induced ...by microgravity bear direct relevance to the safety and viability of these goals, we provide a historical narrative of the urological investigations in space. We review the significant contributions to the understanding of the urologic consequences associated with exposure to microgravity, considerations for prolonged missions, and forward-looking efforts to manage emergent conditions remotely. Historic insights gleaned are poised to inform inter-planetary travel, where urologic pathology will remain an important practical consideration.
Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these ...high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent.
This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging.
Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression.
Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.
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