David H.W. Lau

Increasing prostate biopsy cores based on volume vs the sextant biopsy: a prospective randomized controlled clinical study on cancer detection rates and morbidity

To determine if a volume‐adjusted increase in the number of biopsy cores could detect more prostate cancers than the standard sextant biopsy alone, without increasing morbidity, and to determine its applicability in Malaysian patients, as a standard sextant biopsy misses 20–25% of prostate malignancies.

The Management of Phosphodiesterase-5 (PDE5) Inhibitor Failure

The oral phosphodiesterase type 5 (PDE5) inhibitors have made a valuable contribution to the treatment of erectile dysfunction (ED). PDE5 inhibitors enhance cavernosal smooth muscle relaxation, vasodilatation and penile erection. However, PDE5 inhibitors are not always effective. Decreased efficacy, cost, incorrect administration, lack of sexual stimulation, vascular risk factors associated with ED and vascular or neurogenic diseases are causes of PDE5 inhibitor failure. Tachyphylaxis may also occur. This is defined as reduced tissue responsiveness to a drug in the presence of a constant concentration of this drug. Treatment failure may cause considerable distress. If dose titration, more attempts and continuous dosing of PDE5 inhibitors (taken on a daily basis) fail to resolve the initial PDE5 inhibitor failure, clinicians need to consider alternative treatments. These include sublingual apomorphine, intracavernosal/intraurethral pharmacotherapy, vacuum devices, the insertion of a prosthesis and penile vascular surgery. Combination therapy like prostaglandin E(1) (PGE(1)) with doxazosin (dox; an alpha-1-blocker) or ketanserin (ketan; a 5-HT(2) antagonist) as well as other pro-erection agents, like Endothelin-1 antagonists, angiotensin II antagonists (valsartan/losartan), adrenomedullin, Rho kinase inhibitors and nitric oxide (NO) donors may be beneficial in the treatment of ED. However, these combination therapies need to be validated. Adding an androgen to a PDE5 inhibitor may help when circulatory testosterone levels are low. The early use of PDE5 inhibitors in patients with hypertension, hyperlipidaemia or diabetes with concomitant ED and treating these risk factors may improve corporeal blood flow and lead to long-term preservation of cavernosal function. Therefore, the efficacy of PDE5 inhibitors may be maintained. Targeting the risk factors of ED (similar to those for arteriosclerosis) in the early stages of the disease may prevent the development or decrease the severity of ED.

Serotonin Induces a Biphasic Response in Rabbit Cavernosal Smooth Muscle: Relevance to the Erectile Process

Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT. Methods: Organ bath studies were used. Results: 5-HT induced a sustained contraction occasionally accompanied by a transient relaxation (in 30% of rabbit cavernosal tissues) that preceded the contraction. Ondansetron and Y-25130 (both 5-HT3 receptor antagonists) but not SB-269970 (a 5-HT7 receptor antagonist) significantly inhibited or abolished this transient relaxation. Doxazosin (dox, an α1-receptor antagonist) and ketanserin (ketan, a 5-HT2A receptor antagonist) significantly inhibited or abolished the sustained contraction. The effects of dox on 5-HT-mediated contraction were concentration-dependent. Conclusions: Our findings further confirm that the peripheral serotonergic pathway may play a part in the erectile process via 5-HT2A receptor-mediated contractile and 5-HT3 receptor-mediated relaxant activities. Our results also support the findings of human studies, which suggest that both ketan and dox may exert beneficial effects on the erectile process.

In vivo and in vitro response of corpus cavernosum to phosphodiesterase-5 inhibition in the hypercholesterolaemic rabbit.

Concerning the management of the nine patients reported by Pepper et al. , the diagnostic and therapeutic criteria for managing suspected lymphoceles were neither defined nor standardised. Some patients were actively treated, others not, but the criteria on which these decision were based are unclear. Thus an evaluation of the chosen strategies is impossible. Also, the case number of nine lymphoceles, apart from representing a gross underestimation of the true incidence of lymphoceles, would be rather small for determining ‘the best method of diagnosis and treatment’.