Among men with prostate cancer who were randomly assigned to radical prostatectomy or observation and followed for a median of 12.7 years, overall survival was not significantly increased by surgery.
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, ...the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.
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•Protein-restricted (PR) and branched-chain amino acid (BCAA)-restricted diets improve metabolic health•Decreasing dietary BCAAs recapitulates many of the benefits of a PR diet•Low BCAA diet improves metabolic health independently from changes in energy balance•Dietary protein quality regulates metabolic health independently from protein quantity
Protein-restricted (PR) diets improve metabolic health in mice. Fontana et al. find that PR diets improve metabolic health in humans and that a specific reduction in the consumption of three branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—by mice improves many aspects of glycemic control and body composition to the same extent as reducing all dietary amino acids.
Dutasteride, an inhibitor of 5α-reductase in the prostate, was tested in a large, randomized trial to determine its ability to prevent prostate cancer. Over the 4 years of the trial, dutasteride, as ...compared with placebo, reduced the relative risk of biopsy-detected prostate cancer by 23%. The reduction was limited mainly to tumors with Gleason scores of 5 or 6; by year 4, there were 12 tumors with Gleason scores of 8 to 10 in the dutasteride group but only 1 in the placebo group.
Dutasteride, an inhibitor of 5α-reductase in the prostate, reduced the relative risk of biopsy-detected prostate cancer by 23%; however, the reduction was limited mainly to tumors with Gleason scores of 5 or 6.
The 5α-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and may reduce the risk of prostate cancer.
1
The results of the Prostate Cancer Prevention Trial showed that finasteride, as compared with placebo, reduced the risk of prostate cancer by 25%, but among the tumors that were detected, there was a 27% increase in the number of those that had Gleason scores of 7 to 10.
2
(The Gleason score is the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a . . .
Although prostate-specific antigen (PSA) screening has improved the detection of prostate cancer, allowing for stage migration to less advanced disease, the precise mortality benefit of early ...detection is unclear. This is in part due to a discrepancy between the two large randomized controlled trials comparing PSA screening to usual care. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a survival benefit to screening, while the United States Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial did not. Furthermore, the benefit of immediate surgical intervention for screen-detected prostate cancer is unclear, as the results superficially differ between the two large randomized controlled trials comparing prostatectomy to observation. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found no survival benefit for prostatectomy in PSA screened U.S. men, while the Scandinavian Prostate Cancer Group Study Number Four (SPCG-4) found a survival benefit for prostatectomy in clinically diagnosed prostate cancer. As a result of the controversy surrounding PSA screening and subsequent prostate cancer treatment, guidelines vary widely by organization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Estimates of prostate cancer-specific mortality (PCSM) were similar for men randomly assigned to intervention compared with usual care on the Prostate, Lung, Colorectal and Ovarian PC screening ...study. However, results analyzed by comorbidity strata remain unknown.
Between 1993 and 2001, of 76,693 men who were randomly assigned to usual care or intervention at 10 US centers, 73,378 (96%) completed a questionnaire that inquired about comorbidity and prostate-specific antigen (PSA) testing before random assignment. Fine and Gray's multivariable analysis was performed to assess whether the randomized screening arm was associated with the risk of PCSM in men with no or minimal versus at least one significant comorbidity, adjusting for age and prerandomization PSA testing.
After 10 years of follow-up, 9,565 deaths occurred, 164 from PC. A significant decrease in the risk of PCSM (22 v 38 deaths; adjusted hazard ratio AHR, 0.56; 95% CI, 0.33 to 0.95; P = .03) was observed in men with no or minimal comorbidity randomly assigned to intervention versus usual care, and the additional number needed to treat to prevent one PC death at 10 years was five. Among men with at least one significant comorbidity, those randomly assigned to intervention versus usual care did not have a decreased risk of PCSM (62 v 42 deaths; AHR, 1.43; 95% CI, 0.96 to 2.11; P = .08).
Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment.
BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that ...delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer.
In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849.
Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3–4 study drug-related adverse event (two 1% of 157 patients, both grade 3), and there were no treatment-related deaths.
Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state.
FKD Therapies Oy.
Over 700 men were assigned to radical prostatectomy or observation after receiving a diagnosis of prostate cancer, usually on the basis of elevated PSA levels. After a median of 10 years, ...between-group differences in all-cause and prostate-cancer mortality were not significant.
The treatment of early-stage prostate cancer remains controversial, especially for tumors detected by means of prostate-specific antigen (PSA) testing.
1
Systematic reviews have provided inadequate information for assessing the comparative effectiveness of treatments and any associated harms.
2
Although the lifetime risk of receiving a diagnosis of prostate cancer is about 17%, the risk of dying from the disease is approximately 3%, suggesting that conservative management may be appropriate for many men.
3
,
4
Two randomized trials compared radical prostatectomy with observation but were conducted before PSA testing became widespread.
5
,
6
One study failed to show a significant difference in overall mortality after . . .
Background
The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality ...from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
Methods
A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results
Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P
interaction = .81), pretrial PSA testing (P
interaction = .52), and comorbidity (P
interaction = .68).
Conclusions
After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
Management of Benign Prostatic Hyperplasia Kim, Eric H; Larson, Jeffrey A; Andriole, Gerald L
Annual review of medicine,
01/2016, Letnik:
67, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone ...balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy.
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