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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radical prostatectomy (RP) remains the standard treatment for men with clinically localized prostate cancer, despite the range of alternative treatment modalities. Even with significant advances in surgical technique and superb results for cancer control and preservation of urinary function, erectile dysfunction (ED) following RP is a common complication. This is mainly attributed to temporary cavernous nerve damage (neuropraxia) resulting in penile hypoxia, smooth muscle apoptosis, fibrosis and veno-occlusive dysfunction. One of the most promising new approaches is the concept of early penile rehabilitation, which is thought to prevent ED after RP by countering post-RP pathophysiological changes during the period of neural recovery. Various treatments, such as vacuum constriction devices, intraurethral and intracorporal alprostadil, and phosphodiesterase type 5 (PDE5) inhibitors, might serve to facilitate recovery of erectile function. PDE5 inhibitors are considered as the first-line treatment for early penile rehabilitation, with superior erectile function outcomes compared to placebo. Definitive conclusions regarding the success of penile rehabilitation cannot be drawn at this time because of differences in study design, data acquisition, and definitions of potency. Continued prospective, rigorous study is needed to develop and bring forward this important field and to establish the best evidence basis for counseling and treating patients suffering from ED after RP.
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PMID:Erectile dysfunction following prostatectomy: prevention and treatment. 1965 76

To review the current literature regarding the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), and the role of phosphodiesterase-5 (PDE5) inhibitors for the treatment of LUTS. Review of recently published (1990-2009) data regarding epidemiologic and pathophysiologic mechanisms are involved in LUTS-ED, focusing on PDE5 inhibitors particularly evidenced from level 1 clinical trials. Search terms included phosphodiesterase inhibitors, nitric oxide, autonomic hyperactivity, Rho-kinase, atherosclerosis, LUTS, benign prostatic hypertrophy, and ED. Results of several epidemiologic studies show a possible causal relationship between LUTS and ED. Four possible mechanisms have been proposed to explain this association. Multiple large clinical trials have shown a benefit in LUTS after PDE5-inhibitors treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment.
Prostate Cancer Prostatic Dis 2009
PMID:PDE5 inhibitors for LUTS. 1968 1

Erectile dysfunction (ED) is one of the most challenging complications associated with radical prostatectomy (RP) for clinically localized prostate cancer. Currently, a broad spectrum of therapeutic options are available to improve sexual health after surgical treatment. Several basic science reports highlighted a potential role for phosphodiesterase type 5 inhibitors in the prevention of endothelial damage related to ischemia reperfusion and/or denervation following surgery. Recent studies have shown that pharmacological prophylaxis soon after RP can significantly improve the rate at which erectile function is recovered after surgery. Use of on-demand treatments for ED in patients who have undergone RP has been shown to be highly effective. In this context, pharmacological prophylaxis potentially may have a significantly expanded role in future strategies aimed at preserving postoperative erectile function. We analyzed the factors affecting erectile function after RP and evaluated the evidence suggesting the role of pharmacological prophylaxis and treatment of ED after surgery.
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PMID:Prophylaxis of erectile function after radical prostatectomy with phosphodiesterase type 5 inhibitors. 1986 Jun 95

As a long-acting phosphodiesterase type 5 (PDE5) inhibitor, tadalafil is administered orally as the first line therapy for erectile dysfunction (ED). Its efficacy and safety have been confirmed by many clinical studies in the treatment of ED in general patients, elderly patients and those with diabetes mellitus or spinal cord injury or after prostate cancer surgery. With its prolonged action of 36 hours, tadalafil can not only increase the self-esteem of ED men but also improve the quality of life of both the patients and their partners.
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PMID:[Efficacy and safety of tadalafil for erectile dysfunction: an updated review]. 2011 48

Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer.
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PMID:Randomised, placebo-controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer. 2059 10

We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induced apoptosis in PC-3 and DU145 prostate cancer cells, which was mediated by enhanced generation of reactive oxygen species, up-regulation of caspase-3 and caspase-9 activities, reduced expression of Bcl-xL, and phosphorylation of Bad. Overexpression of Bcl-xL or dominant negative caspase 9 attenuated the synergistic effect of sildenafil and DOX on prostate cancer cell killing. Furthermore, treatment with sildenafil and DOX in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. The reduced tumor size was associated with amplified apoptotic cell death and increased expression of activated caspase 3. Doppler echocardiography showed that sildenafil treatment ameliorated DOX-induced left ventricular dysfunction. In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit.
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PMID:Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction. 2088 55

Management of adverse events related to cancer therapies are seen as tertiary prevention. Concerning prostate cancer, dealing with secondary effects of treatments is crucial. Indeed, if recent advances in cancer therapy have lead to an acceptable overall prognosis, these results face increasing cases of adverse events that can dramatically impact quality of life. Localized prostate cancer management (by radical prostatectomy, brachytherapy, external radiation therapy, hormonal treatment) leads to two main secondary effects: bladder and urinary sphincter dysfunction on one hand and sexual disorders on the other hand. Urinary disorders are stress urinary incontinence (mainly after radical prostatectomy), storage symptoms and overactive bladder, and outflow obstruction (mainly after radiation therapy). Stress urinary incontinence can be managed by pelvic floor muscle training and behavioural treatment. In case of failure, and after one year of evolution, surgical options are indicated (periurethral injections, artificial urinary sphincter, tapes and balloons). Storage symptoms respond to medical management (anticholinergics), and obstructive symptoms are treated by alpha-blockers, self-catheterization or surgery if necessary. Sexual disorders are erectile dysfunction, pelvic floor discomfort, orgasm disorder, and penile retraction and fibrosis. Available options gather medical treatment by phosphodiesterase-5 inhibitors, Vacuum, and penile prosthesis. Recent advances in this field point out the role of early penile rehabilitation and prevention of sexual disorders. Although often associated in the same patients, sexual and urinary disorders following prostate cancer management are often considered separately. Their combined treatment should be an objective for both clinical practice and research. New treatments for stress urinary incontinence management (latero-urethral balloons, new male slings) and for erectile dysfunction (penile rehabilitation, treatment penile retraction and optimal use of phosphodiesterase-5 inhibitors) will extend the therapeutic options in the next future, and improve the level of care for patients with prostate cancer.
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PMID:[Urinary and sexual disorders following localised prostate cancer management]. 2122 Feb 29

Radical prostatectomy (RP) is a commonly performed procedure for the management of prostate cancer. While documented oncologic outcome for early stage disease is excellent, functional impairments such as incontinence and erectile dysfunction (ED) are common after the procedure. Recent evidence has implicated cavernous nerve damage and subsequent corporal oxygen deprivation, as well as corporal inflammation, in the pathogenesis of post-RP ED. Targeted therapies such as oral phosphodiesterase-5 inhibitors, mechanical vacuum erection devices, local alprostadil delivery and testosterone replacement (for hypogonal patients) have demonstrated some efficacy in the management of post-RP ED. This review aggregates much of the recent data in support of these therapies and critically reviews them. The article then presents tools to assess patients and partner sexual function to aid in identifying and monitoring post-RP ED. Finally, the article describes a protocol in use at Baylor College of Medicine as a guide toward the development of a protocol for erectile preservation (EP). The purpose of this work is to educate clinicians on emerging concepts in EP and provide an implementable protocol for use in practice.
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PMID:Emerging concepts in erectile preservation following radical prostatectomy: a guide for clinicians. 2169 60

Prostate cancer is the most common cancer among men, representing approximately 25% of all new cancer diagnoses in the USA. For clinically localized prostate cancer, the gold standard for therapy remains radical prostatectomy. One of the main adverse effects of this procedure is erectile dysfunction, which can have a significant impact on the patient's quality of life. There are several mechanisms of erectile dysfunction postprostatectomy, including arteriogenic, venogenic and neurogenic types, as well as the potentially heightened risk of postprostatectomy patients to develop Peyronie's disease. The purpose of this review is to explain the various treatment options available, including phosphodiesterase type 5 inhibitors, intracavernosal injections, intraurethral alprostadil suppositories, vacuum erection devices, and penile prostheses. The role of these therapies in an erectile-dysfunction-treatment function, as well as in penile rehabilitation, will be discussed. Finally, a review of research on novel therapies will also be presented. A comprehensive literature review was performed using the PubMed database. Articles were chosen based on topical relevance and assessed for methodology and major findings. There are data to support the use of each of the therapeutic options in both treatment and rehabilitative roles. More study is needed, however, specifically in regard to penile rehabilitation, to confirm its benefits, as well as to determine optimal rehabilitation protocols.
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PMID:Erectile preservation following radical prostatectomy. 2178 97

Evidence supporting an early origin of prostate cancer is growing. We demonstrated previously that brief exposure of neonatal rats to estradiol or bisphenol A elevated their risk of developing precancerous lesions in the prostate upon androgen-supported treatment with estradiol as adults. Epigenetic reprogramming may be a mechanism underlying this inductive event in early life, because we observed overexpression of phosphodiesterase 4D variant 4 (Pde4d4) through induction of hypomethylation of its promoter. This epigenetic mark was invisible in early life (postnatal d 10), becoming apparent only after sexual maturation. Here, we asked whether other estrogen-reprogrammable epigenetic marks have similar or different patterns in gene methylation changes throughout life. We found that hypomethylation of the promoter of nucleosome binding protein-1 (Nsbp1), unlike Pde4d4, is an early and permanent epigenetic mark of neonatal exposure to estradiol/bisphenol A that persists throughout life, unaffected by events during adulthood. In contrast, hippocalcin-like 1 (Hpcal1) is a highly plastic epigenetic mark whose hypermethylation depends on both type of early-life exposure and adult-life events. Four of the eight genes involved in DNA methylation/demethylation showed early and persistent overexpression that was not a function of DNA methylation at their promoters, including genes encoding de novo DNA methyltransferases (Dnmt3a/b) and methyl-CpG binding domain proteins (Mbd2/4) that have demethylating activities. Their lifelong aberrant expression implicates them in early-life reprogramming and prostate carcinogenesis during adulthood. We speculate that the distinctly different fate of early-life epigenetic marks during adulthood reflects the complex nature of lifelong editing of early-life epigenetic reprogramming.
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PMID:Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life. 2210 88


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