Majid Shabbir

Purinergic receptor-mediated effects of adenosine 5′-triphosphate in urological malignant diseases

Adenosine 5′‐triphosphate (ATP) mediates a variety of biological functions and has been shown to play a physiological role in almost every system in the body. In the genito‐urinary system, extracellular ATP has been shown to play a functional role in several different capacities, ranging from nociception in the ureter and bladder, to erectile dysfunction via its action on different ‘purinergic receptors’. Discovery of the trophic effects of ATP has led to a surge in interest in this signalling system in various malignancies. To date five P2 receptor subtypes have been implicated in the growth inhibition of cancer cells, namely P2X5, P2X7, P2Y1, P2Y2 and P2Y11. Limited data are available on urological malignancies. ATP induces its anti‐neoplastic effect primarily via purinergic receptor‐mediated apoptosis via calcium‐independent pathways, and this has been confirmed in vitro and in vivo. Studies have highlighted functional roles for the P2X5 and/or P2Y11 receptors in both hormone refractory prostate cancer and high‐grade bladder cancer, although the contributory effect of pro‐apoptotic P2X7 receptors remains unclear. Clinical trials have shown intravenous ATP successfully attenuates a range of systemic symptoms associated with advanced malignancies. This raises the possibility that selective targeting of specific aberrant pathways may allow for treatment of advanced primary malignancies and their systemic effects.

Purinergic receptor‐mediated effects of ATP in high‐grade bladder cancer

To assess whether the antineoplastic action of extracellular ATP seen in hormone‐refractory prostate cancer extends to other aggressive urological malignancies by investigating its effect in high‐grade bladder cancer cells in vitro and in vivo.

Effect of extracellular ATP on the growth of hormone-refractory prostate cancer in vivo.

To investigate whether the antineoplastic action of ATP on hormone‐refractory prostate carcinoma (HRPC) cells in vitro also occurs in vivo, by examining the effect of ATP in vivo on tumours resulting from implanted HRPC cells in mice.

Characterization of calcium-independent purinergic receptor-mediated apoptosis in hormone-refractory prostate cancer.

To investigate the nature of purinergic signalling in hormone‐refractory prostate cancer (HRPC) cells in vitro, as extracellular ATP inhibits the growth of HRPC in vitro via the activation of P2 purinergic receptors, and to characterize which P2 receptors subtypes and secondary mechanisms are involved.

Therapeutic strategies for patients with micropenis or penile dysmorphic disorder.

Micropenis in adults is defined as a stretched length of <7.5 cm. Many aetiologies exist, including congenital and endocrinological causes as well as pathological conditions, such as penile lichen sclerosus, trauma and genital cancer. The resulting reduction in functional penile length can lead to considerable psychosexual morbidity. Furthermore, the subset of patients with micropenis who also suffer from penile dysmorphic disorder require careful and intensive psychological counselling. Corrective surgery for micropenis can be performed in patients with realistic expectations. Total phalloplasty using radial-artery-based forearm skin flaps can offer restoration of normal penile length in selected patients. More-conservative surgical techniques to improve length or girth are limited by minimal enhancement but associated with a significantly lower rate of complications and comorbidity compared to total phalloplasty. Emerging tissue engineering techniques might represent a suitable alternative to penile replacement surgery in the future.

Diagnosis and management of premalignant penile lesions

Diagnosing premalignant penile lesions from benign penile dermatoses presents a unique challenge. The rarity of these conditions and the low incidence of penile cancer mean that the majority of our knowledge is based on small, non-randomized, retrospective studies. The introduction of specialist penile cancer centres in the UK has resulted in the centralization of expertise and resources, and has furthered our understanding of the biological behaviour and management of this rare malignancy. We review the current trends in the approach to diagnosing and treating various premalignant penile conditions.

Challenges and controversies in the management of penile cancer

Penile cancer is a rare disease, accounting for ∼1% of all malignancies in men. Poor awareness of the condition among the public and clinicians often causes long delays in diagnosis and treatment, which may result in the development of advanced disease that might require extensive and emasculating surgery. In the UK, the development of supraregional penile cancer centres has pooled resources and expertise, which has led to considerable improvements in our understanding and management of this rare condition over the past decade. However, significant gaps in our knowledge still exist. Several areas of diagnosis and management remain areas of controversy, ranging from preventive strategies and treatment of premalignant disease to the assessment of lymph node involvement and the management of advanced disease.

Male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition: a meta‐analysis

We aimed to assess male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition in heterosexual and homosexual men using all available data. A systematic literature review was conducted searching for studies that assessed male circumcision as a method to prevent HIV acquisition in homosexual and/or heterosexual men. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched in March 2017. A random effects model was used to calculate a pooled risk ratio (RR) and its associated 95% confidence interval (CI). In total, 49 studies were included in this meta‐analysis. The overall pooled RR for both homosexual and heterosexual men was 0.58 (95% CI 0.48–0.70), suggesting that circumcision was associated with a reduction in HIV risk. Circumcision was found to be protective for both homosexual and heterosexual men (RR: 0.80, 95% CI 0.69–0.92 and 0.28, 95% CI 0.14–0.59, respectively). Heterosexual men had a greater RR reduction (72% compared with 20% for homosexual men). There was significant heterogeneity among the studies (χ2 = 1378.34, df = 48; I2 = 97%). This meta‐analysis shows that male circumcision was effective in reducing HIV risk for both heterosexual and homosexual men.

British Association of Urological Surgeons (BAUS) consensus document for the management of male genital emergencies ‐ testicular trauma

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on‐site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus comprising British Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral Surgery together with experts from units throughout the UK. Testicular trauma requires prompt investigation and treatment in order to prevent the development of subfertility or hypogonadism. This series of consensus statements provide guidance for UK practice.

BAUS consensus document for the management of male genital emergencies: priapism

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on‐site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the BAUS Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Priapism requires prompt assessment and treatment and these consensus statements provide guidance for UK practice.