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Tissue Expression of Androgen Receptor Splice Variant 7 at Radical Prostatectomy Predicts Risk of Progression in Untreated Nonmetastatic Prostate Cancer.
Sciarra, A, Maggi, M, Salciccia, S, Nicolai, A, Tortorella, E, Giantulli, S, Magliocca, FM, Silvestri, I, Taglieri, L, Cattarino, S, et al
Oncology. 2021;(4):251-255
Abstract
BACKGROUND Androgen receptor splice variant V7 (AR-V7) was recently detected in circulating tumor cells of castration-resistant prostate cancer (PC) patients and its expression correlated with resistance to new-generation androgen signaling inhibitors. OBJECTIVES We retrospectively analyzed whether AR-V7 expression was detectable on radical prostatectomy (RP) specimens of untreated nonmetastatic PC cases, and whether it could be associated with progression after surgery. METHOD The expression of AR-V7 and AR-FL (full length) was separately evaluated by immunohistochemistry using a streptavidin-biotin-peroxidase system with 2 anti-AR-V7 and anti-AR-FL rabbit monoclonal antibodies. RESULTS 56 PC cases, classified by their clinical risk, were analyzed. Positive expression was found in 24/32 cases in the high-risk group, 4/13 in the intermediate-risk group, and only 2/11 in the low-risk group. We found a significant correlation between AR-V7 positivity and both risk classification (p < 0.001) and progression after surgery (p < 0.001). CONCLUSIONS In our population of untreated nonmetastatic PC, AR-V7 is detectable by immunohistochemistry in more than 50% of cases. At this early stage, AR-V7 positivity is associated with risk classification and it can predict progression after surgery.
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Hemodynamic, renal and hormonal effects of lung protective ventilation during robot-assisted radical prostatectomy, analysis of secondary outcomes from a randomized controlled trial.
Høyer, S, Mose, FH, Ekeløf, P, Jensen, JB, Bech, JN
BMC anesthesiology. 2021;(1):200
Abstract
BACKGROUND Lung protective ventilation with low tidal volume (TV) and increased positive end-expiratory pressure (PEEP) can have unfavorable effects on the cardiovascular system. We aimed to investigate whether lung protective ventilation has adverse impact on hemodynamic, renal and hormonal variables. METHODS In this randomized, single-blinded, placebo-controlled study, 24 patients scheduled for robot-assisted radical prostatectomy were included. Patients were equally randomized to receive either ventilation with a TV of 6 ml/IBW and PEEP of 10 cm H2O (LTV-h.PEEP) or ventilation with a TV of 10 ml/IBW and PEEP of 4 cm H2O (HTV-l.PEEP). Before, during and after surgery, hemodynamic variables were measured, and blood and urine samples were collected. Blood samples were analyzed for plasma concentrations of electrolytes and vasoactive hormones. Urine samples were analyzed for excretions of electrolytes and markers of nephrotoxicity. RESULTS Comparable variables were found among the two groups, except for significantly higher postoperative levels of plasma brain natriuretic peptide (p = 0.033), albumin excretion (p = 0.012) and excretion of epithelial sodium channel (p = 0.045) in the LTV-h.PEEP ventilation group compared to the HTV-l.PEEP ventilation group. In the combined cohort, we found a significant decrease in creatinine clearance (112.0 [83.4;126.7] ml/min at baseline vs. 45.1 [25.4;84.3] ml/min during surgery) and a significant increase in plasma concentrations of renin, angiotensin II, and aldosterone. CONCLUSION Lung protective ventilation was associated with minor adverse hemodynamic and renal effects postoperatively. All patients showed a substantial but transient reduction in renal function accompanied by activation of the renin-angiotensin-aldosterone system. TRIAL REGISTRATION ClinicalTrials, NCT02551341 . Registered 13 September 2015.
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A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2).
Freedland, SJ, Allen, J, Jarman, A, Oyekunle, T, Armstrong, AJ, Moul, JW, Sandler, HM, Posadas, E, Levin, D, Wiggins, E, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;(12):3035-3043
Abstract
PURPOSE Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer. EXPERIMENTAL DESIGN We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m2 and PSADT 3 to 36 months. The LCD arm was instructed to eat [Formula: see text]20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet. RESULTS Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-seven LCD and 18 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (-117 vs. 8 g, P < 0.001) and lost weight (-12.1 vs. -0.50 kg, P < 0.001). The LCD arm reduced HDL, triglycerides, and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (21 months) and control (15 months, P = 0.316) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, P = 0.021) arms. Adverse events were few, usually mild, and returned to baseline by 6 months. CONCLUSIONS Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.
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Does trunk muscle training with an oscillating rod improve urinary incontinence after radical prostatectomy? A prospective randomized controlled trial.
Heydenreich, M, Puta, C, Gabriel, HH, Dietze, A, Wright, P, Zermann, DH
Clinical rehabilitation. 2020;(3):320-333
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Abstract
OBJECTIVE To investigate the effect of a new therapeutic approach, using an oscillating rod to strength the pelvic floor and deep abdominal musculature and to speed up recovery of continence after radical prostatectomy. DESIGN Prospective randomized controlled clinical trial. SETTING Inpatient uro-oncology rehabilitation clinic. SUBJECTS Ninety-three (intervention group (IG)) and ninety-one patients (control group (CG)) with urinary incontinence after prostatectomy were examined. INTERVENTION All patients were randomly allocated to either standard pelvic floor muscle exercises and oscillating rod therapy (IG) or standard pelvic floor muscle exercises and relaxation therapy (CG). MAIN OUTCOME MEASURES Urinary incontinence (1- and 24-hour pad test) was assessed, and health-related quality of life (HRQL; Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire) was measured for all patients before and after three weeks of treatment. RESULTS One hundred and eighty-four patients (mean (SD) age: 64.1 (6.94) years) completed the study. The IG showed a significant reduction in urinary incontinence (1-hour pad test: P = 0.008, 24-hour pad test: P = 0.012) and a significant improvement of HRQL (P = 0.017) compared with CG. Continence was significantly improved in both groups (1-hour pad test: 22.6-8.5 g (IG) vs. 23.0-18.1 g (CG)/24-hour pad test: 242.9-126.7 g (IG) vs. 237.6-180.9 g (CG)). CONCLUSION The study demonstrated that a combination of conventional continence exercises and the new oscillation rod training increased abdominal and pelvic floor musculature and speeded up recovery of continence after radical prostatectomy.
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Phase II randomised control feasibility trial of a nutrition and physical activity intervention after radical prostatectomy for prostate cancer.
Hackshaw-McGeagh, LE, Penfold, C, Shingler, E, Robles, LA, Perks, CM, Holly, JMP, Rowe, E, Koupparis, A, Bahl, A, Persad, R, et al
BMJ open. 2019;(11):e029480
Abstract
OBJECTIVE Dietary factors and physical activity may alter prostate cancer progression. We explored the feasibility of lifestyle interventions following radical prostatectomy for localised prostate cancer. DESIGN Patients were recruited into a presurgical observational cohort; following radical prostatectomy, they were offered randomisation into a 2×3 factorial randomised controlled trial (RCT). SETTING A single National Health Service trust in the South West of England, UK. PARTICIPANTS Those with localised prostate cancer and listed for radical prostatectomy were invited to participate. RANDOMISATION Random allocation was performed by the Bristol Randomised Trial Collaboration via an online system. INTERVENTIONS Men were randomised into both a modified nutrition group (either increased vegetable and fruit, and reduced dairy milk; or lycopene supplementation; or control) and a physical activity group (brisk walking or control) for 6 months. BLINDING Only the trial statistician was blind to allocations. PRIMARY OUTCOME MEASURES Primary outcomes were measures of feasibility: randomisation rates and intervention adherence at 6 months. Collected at trial baseline, three and six months, with daily adherence reported throughout. Our intended adherence rate was 75% or above, the threshold for acceptable adherence was 90%. RESULTS 108 men entered the presurgical cohort, and 81 were randomised into the postsurgical RCT (randomisation rate: 93.1%) and 75 completed the trial. Of 25 men in the nutrition intervention, 10 (40.0%; 95% CI 23.4% to 59.3%) adhered to the fruit and vegetable recommendations and 18 (72.0%; 95% CI 52.4% to 85.7%) to reduced dairy intake. Adherence to lycopene (n=28), was 78.6% (95% CI 60.5% to 89.8%), while 21/39 adhered to the walking intervention (53.8%; 95% CI 38.6% to 68.4%). Most men were followed up at 6 months (75/81; 92.6%). Three 'possibly related' adverse events were indigestion, abdominal bloating and knee pain. CONCLUSIONS Interventions were deemed feasible, with high randomisation rates and generally good adherence. A definitive RCT is proposed. TRIAL REGISTRATION NUMBER ISRCTN 99048944.
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Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy-A Randomized, Double-blind, Placebo-controlled Clinical Trial.
Murtola, TJ, Syvälä, H, Tolonen, T, Helminen, M, Riikonen, J, Koskimäki, J, Pakarainen, T, Kaipia, A, Isotalo, T, Kujala, P, et al
European urology. 2018;(6):697-701
Abstract
We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change -0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this. PATIENT SUMMARY Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.
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Chryseobacterium gleum in a man with prostatectomy in Senegal: a case report and review of the literature.
Arouna, O, Deluca, F, Camara, M, Fall, B, Fall, B, Ba Diallo, A, Docquier, JD, Mboup, S
Journal of medical case reports. 2017;(1):118
Abstract
BACKGROUND Here we report a rare case of a urinary tract infection due to Chryseobacterium gleum. This widely distributed Gram-negative bacillus is an uncommon human pathogen and is typically associated with health care settings. CASE PRESENTATION We describe a case of urinary tract infection caused by Chryseobacterium gleum in a 68-year-old man of Wolof ethnicity (an ethnic group in Senegal, West Africa) who presented to our Department of Urology in a university teaching hospital (Hôpital Aristide Le Dantec) in Dakar, Senegal, 1 month after prostatectomy. The strain isolated from a urine sample was identified as Chryseobacterium gleum by mass spectrometry (Vitek matrix-assisted laser desorption/ionization, time-of-flight, bioMérieux) and confirmed by 16S ribosomal ribonucleic acid sequencing. The organism was resistant to a wide range of antibiotics, including carbapenem, due to a resident metallo-β-lactamase gene that shared 99% of amino-acid identity with Chryseobacterium gleum class B enzym. CONCLUSIONS Infection by Chryseobacterium gleum is infrequent, and no such case has been previously reported in Africa. Despite its low virulence, Chryseobacterium gleum should be considered a potential opportunistic and emerging pathogen. Further studies on the epidemiology, pathogenicity, and resistance mechanisms of Chryseobacterium gleum are needed for better diagnosis and management.
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Safety and Efficacy of Thulium Laser Prostatectomy Versus Transurethral Resection of Prostate for Treatment of Benign Prostate Hyperplasia: A Meta-Analysis.
Jiang, H, Zhou, Y
Lower urinary tract symptoms. 2016;(3):165-70
Abstract
OBJECTIVE The aim of the present study was to objectively evaluate the safety and efficacy of Thulium laser prostatectmy (TmLRP) versus transurethral resection of prostate (TURP) in treating benign prostate hyperplasia (BPH). METHODS Online databases such as Cochrane Library, PubMed, Embase, and Chinese biomedicine literature database were searched by randomized control trial (RCT), quasi-randomized control trial (Q-RCT) and case control study (CCSs) about TmLRP versus TURP for the treatment of BPH. After study selection, assessment and data extraction conducted, Meta-analyses were performed by using the RevMan 5.2 software. RESULTS Six studies involving 640 patients were included and the results of follow-up time was 1 year. The results of meta-analyses showed that: (i) safety indicators: compared with TURP, TmLRP was associated with less decrease of serum sodium salt, less blood transfusion, shorter catheterization time hospital time and more operation time. No differences were noted in the TUR syndrome, recatheterization rate, transitory urge incontinence, stress incontinence urethral stricture and retrograde ejaculation. (ii) Efficacy indicators (International Prostate Symptom Score [IPSS], post-void residual [PVR], Qmax, quality of life [QoL]): Compared with the baseline, significant improvement in IPSS, QoL, Qmax and PVR were obvious improvement before and after surgery in both groups. There were statistical differences in IPSS at 12 months, QoL at 1, 6 months and Qmax 1, 6 months between the two groups. CONCLUSIONS TmLRP is a safe and effective procedure for treatment of benign prostatic hyperplasia. Compared with TURP, TmLRP was not only associated with less decrease of serum sodium salt, less blood transfusion, shorter catheterization time and hospital time, but also may be superior to TURP in efficacy.
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Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy.
Cipolla, BG, Mandron, E, Lefort, JM, Coadou, Y, Della Negra, E, Corbel, L, Le Scodan, R, Azzouzi, AR, Mottet, N
Cancer prevention research (Philadelphia, Pa.). 2015;(8):712-9
Abstract
Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated "biochemical recurrence." Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 ± 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0-M6) followed by 2 months without treatment (M6-M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (+0.099 ± 0.341 ng/mL) than in placebo (+0.620 ± 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases >20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3-M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy.
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[Laparascopic radical prostatectomy].
Ganzer, R, Do, M, Rai, BP, Dietel, A, Stolzenburg, JU
Der Urologe. Ausg. A. 2015;(2):172-7
Abstract
BACKGROUND Since its initial description 20 years ago, laparoscopic radical prostatectomy (LRP) is now a standard treatment option for localized prostate cancer. However, in recent years robot-assisted laparoscopic radical prostatectomy (RALP) has been gradually replacing LRP, despite high costs incurred with RALP. OBJECTIVES The purpose of this work was to determine the oncological outcomes of LRP from selected series with a follow-up of around 10 years and to compare oncological and functional outcomes between LRP and RALP. MATERIAL AND METHODS The outcomes of a case series of LRP with a median follow-up of at least 3 years were reviewed. In addition, the outcomes of comparative studies between LRP and RALP were reviewed. RESULTS The first case series of LRP with follow-ups of 10 years after LRP are available and show favorable oncologic outcomes. Current data show that RALP offers superior functional results (recovery of erectile function) following bilateral nerve sparing when compared to LRP. CONCLUSION The first review a few years ago showed comparable oncologic and functional outcomes between open prostatectomy, LRP, and RALP. Recent data from comparative studies show superiority of RALP over LRP for potency following bilateral nerve sparing. The potency outcomes between LRP and RALP are, however, similar following wide excision of both neurovascular bundles. Therefore, both treatment options can be recommended for the treatment of localized PC.