Over the last 2 decades the evolution of alpha-blockers for lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) has been to preserve effectiveness, improve tolerability, and ...eliminate dose titration. Today, alpha-blockers represent the first-line treatment of most men with BPH whereby the primary objective is relief from bothersome LUTS.
Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We ...recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Background Increasing evidence supports the use of magnetic resonance (MR)–targeted prostate biopsy. The optimal method for such biopsy remains undefined, however. Objective To prospectively ...compare targeted biopsy outcomes between MR imaging (MRI)–ultrasound fusion and visual targeting. Design, setting, and participants From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences. Intervention Two MRI–ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy. Outcome measurements and statistical analysis Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression. Results and limitations Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum ≥7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting ( p = 0.1374, p = 0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual ( p = 0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum ≥7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited. Conclusions Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose While major prostate cancer active surveillance programs recommend repeat testing such as prostate specific antigen and prostate biopsy, to our knowledge compliance with such testing is ...unknown. We determined whether men in the community receive the same intensity of active surveillance testing as in prospective active surveillance protocols. Materials and Methods We performed a retrospective cohort study of men 66 years old or older in the SEER (Surveillance, Epidemiology and End Results)-Medicare database. These men were diagnosed with prostate cancer from 2001 to 2009, did not receive curative therapy in the year after diagnosis and underwent 1 or more post-diagnosis prostate biopsies. We used multivariable adjusted Poisson regression to determine the association of the frequency of active surveillance testing with patient demographics and clinical features. In 1,349 men with 5 years or less of followup we determined the proportion who underwent testing as intense as that recommended by the Sunnybrook Health Sciences Centre and PRIAS (Prostate Cancer Research International Active Surveillance) programs, including 14 or more PSA tests and 2 or more biopsies, and The Johns Hopkins program, including 10 or more prostate specific antigen tests and 4 or more biopsies. Results Among 5,192 patients undergoing active surveillance greater than 80% had 1 or more prostate specific antigen tests per year but fewer than 13% underwent biopsy beyond the first 2 years. Magnetic resonance imaging was rarely done during the study period. On multivariable analysis recent diagnosis and higher income were associated with a higher frequency of surveillance biopsy while older age and greater comorbidity were associated with fewer biopsies. African American men underwent fewer prostate specific antigen tests but a similar number of biopsies. During 5 years of active surveillance only 11.1% and 5.0% of patients met the testing standards of the Sunnybrook/PRIAS and The Johns Hopkins programs, respectively. Conclusions In the community few elderly men receive the intensity of active surveillance testing recommended in major prospective active surveillance programs.
While magnetic resonance imaging-ultrasound fusion targeted biopsy allows for improved detection of clinically significant prostate cancer, a concerning amount of clinically significant disease is ...still missed. We hypothesized that a number of these misses are due to the learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. We report the results of repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer and the institutional learning curve in the detection of clinically significant prostate cancer with time.
We analyzed the records of 1,813 prostate biopsies in a prospectively acquired cohort of men who presented for prostate biopsy in a 4-year period. All men were offered prebiopsy magnetic resonance imaging and were assigned a maximum PI-RADS™ (Prostate Imaging Reporting and Data System version 2) score. Biopsy outcomes in men with a suspicious region of interest were compared. The relationship between time and clinically significant prostate cancer detection was analyzed.
The clinically significant prostate cancer detection rate increased 26% with time in men with a PI-RADS 4/5 region of interest. On repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer 53% of those with a PI-RADS 4/5 region of interest demonstrated clinically significant discordance from the initial magnetic resonance imaging-ultrasound fusion targeted biopsy compared to only 23% with a PI-RADS 1/2 region of interest. Significantly less clinically significant prostate cancer was missed or under graded in the most recent biopsies compared to the earliest biopsies.
The high upgrade rate on repeat magnetic resonance imaging-ultrasound fusion targeted biopsy and the increasing cancer detection rate with time show the significant learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. Men with low risk or negative biopsies with a persistent, concerning region of interest should be promptly rebiopsied. Improved targeting accuracy with operator experience can help decrease the number of missed cases of clinically significant prostate cancer.
Purpose Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk ...stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. Materials and Methods A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Results Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men the negative predictive value of a combination of negative magnetic resonance imaging with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding biopsy and reducing over detection/overtreatment. Among men with a previous negative biopsy 72% to 87% of cancers detected by magnetic resonance imaging guidance are clinically significant. Among men with a known low risk cancer, repeat biopsy using magnetic resonance targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and of upgrading in high suspicion score lesions. Techniques of magnetic resonance imaging targeted biopsy include visual estimation transrectal ultrasound guided biopsy; software co-registered magnetic resonance imaging-ultrasound, transrectal ultrasound guided biopsy; and in-bore magnetic resonance imaging guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, co-registered magnetic resonance imaging-ultrasound biopsy as well as in-bore magnetic resonance imaging guided biopsy appear to increase cancer detection rates in conjunction with increasing suspicion score. Conclusions Use of magnetic resonance imaging for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact therapeutic decision making. Optimal clinical application of magnetic resonance imaging targeted biopsy remains under investigation.
Several consensus statements recommend serial serum prostate-specific antigen (PSA), multi parametric magnetic resonance imaging (mpMRI), and prostate biopsy following partial gland ablation. We ...determined the rate of persistent in-field disease following primary partial gland cryo-ablation and whether PSA or mpMRI are reliable predictors of in-field disease persistence.
Between March 2017 and July 2019, subjects meeting eligibility criteria for partial gland cryoablation were enrolled into an IRB approved outcomes registry. PSA, mpMRI, and prostate biopsy (four cores targeting the ablation zone + six ipsilateral systematic cores) were performed per protocol 6 months following intervention. Binary logistic regression was employed to calculate odds ratio (OR) of PSA decrease, and suspicious mpMRI effect on cancer persistence. The performance of mpMRI for predicting in-field persistence of PCa was evaluated by area under the receiver operation characteristics curve (AUC).
Of the 83 eligible men undergoing partial gland cryoablation, 70 (84.3%) underwent 6-month protocol prostate biopsy. Five (7.1%) biopsies exhibited any in-field disease persistence. Only one (1.4%) of these cancers was Gleason grade > 1. Neither PSA decrease or suspicious mpMRI reliably predicted cancer persistence, with OR of 1.6 (0.25-8.6) and 1.5 (0.02-1.3), respectively. AUC of mpMRI for predicting in-field disease persistence was 0.554.
In this cohort of patients undergoing partial gland cryo-ablation, the incidence of persistent disease was low. PSA and mpMRI were not reliable predictors of in-field disease persistence. Based on these data, consideration may be given to deferring early follow-up biopsy in appropriate patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives To examine the pathologic findings and biochemical recurrence rates for a consecutive cohort of candidates for active surveillance who underwent radical prostatectomy. The role of active ...surveillance for the treatment of low-risk prostate cancer is highly controversial. Methods Between October 2000 and February 2008, a single surgeon performed 1565 open radical retropubic prostatectomies for clinically localized prostate cancer. Cases were selected for extraction if they fulfilled 1 of 2 published criteria for active surveillance in our prospective longitudinal outcomes database. A retrospective review of the prospectively collected database was executed to elucidate the outcomes of candidates for active surveillance who underwent radical retropubic prostatectomy. Gleason score, pathologic stage, and surgical margins were prospectively captured in our database. The 5-year, biochemical-free survival rates were estimated using Kaplan-Meier analysis plots. Results Overall, 45.9%-47.2% of cases were pathologically upgraded to a Gleason score ≥ 7. Moreover, 12.3%-13.1% of cases were found to have a primary Gleason pattern of 4 or 5. Extracapsular extension (pT3a disease) was observed in 7.8%-10.9% of cases. A total of 28.8%-32.2% of cases had an estimated percentage of cancer volume in the surgical specimen exceeding 20%. The 5-year biochemical-free survival was estimated to be 83.2%-92.9%. Conclusions Our pathologic findings and risk of biochemical recurrence after open radical prostatectomy questions the wisdom of active surveillance in men with low-risk disease who have “long” life expectancies.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives. To evaluate the efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha
1A-antagonist studied in clinical trials.
Methods. Patients with benign prostatic ...hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary efficacy parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary efficacy parameters were improvement in measurements at individual double-blind visits corresponding to the primary efficacy parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric parameters; and investigator’s global assessment.
Results. Statistically significant improvements in all efficacy parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group.
Conclusions. Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK