Showing papers by "Asif Muneer published in 2016"

CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma

Abstract: Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort. Mutation data were also integrated with DNA methylation and copy-number information from the same patients. We identified an HPV-associated APOBEC mutation signature and an NpCpG signature in HPV-negative disease. We also identified recurrent mutations in the novel penile cancer tumor suppressor genes CSN1(GPS1) and FAT1. Expression of CSN1 mutants in cells resulted in colocalization with AGO2 in cytoplasmic P-bodies, ultimately leading to the loss of miRNA-mediated gene silencing, which may contribute to disease etiology. Our findings represent the first comprehensive analysis of somatic alterations in penile cancer, highlighting the complex landscape of alterations in this malignancy.

Semen characteristics in consecutive ejaculates with short abstinence in subfertile males

Abstract: This study reports the favourable semen characteristics of 73 subfertile oligozoospermic men with short abstinence periods up to 40 min. Semen characteristics were compared between initial and consecutive ejaculate showing improved semen parameters: progressive grade A spermatozoa, morphology and sperm concentration. Median concentrations in initial and consecutive ejaculates were 10 million/ml and 17 million/ml, respectively. The second sample had a higher median normal morphology (7% versus 6%, P < 0.001). The median of non-progressive spermatozoa (Grade C) was significantly lower in the consecutive sample than the initial sample (0% versus 5%, P < 0.01). Medians for slow progression spermatozoa (B grade) and immotile spermatozoa (D grade) were lower in the consecutive samples (20% versus 13%, P < 0.01 and 60% versus 50%, P < 0.001, respectively). The median for rapid motility (Grade A) was significantly higher in the consecutive sample than the first (30% versus 5%, P < 0.001). Overall median progressive motility as benchmarked by the WHO 2010 criteria was significantly higher in the consecutive sample (43% versus 25%, P < 0.001). Semen analyses of consecutive semen samples collected 30 min (mean) apart in oligozoospemic men should be checked routinely for diagnostic purposes and for managing potential subfertility treatment.

An update on the diagnosis and management of ejaculatory duct obstruction

Abstract: Ejaculatory duct obstruction (EDO) remains a rare but surgically correctable cause of male sexual dysfunction and male infertility due to obstructive azoospermia, diagnosed in up to 5% of infertile men. EDO should, therefore, be considered within the list of differential diagnoses for men undergoing infertility investigations, with work up including clinical examination, transurethral ultrasonography, semen analysis, chromotubation, seminal vesiculography and seminal vesicle aspiration. Obstruction can be limited to the distal ends of the ducts or it can extend proximally to include the terminal portions of the vasa deferentia, with the site and length of the obstruction having implications for surgical intervention. Early endoscopic treatment can reverse symptoms and prevent the progression of partial obstruction to bilateral, complete obstruction, and transurethral resection of the ejaculatory duct remains the main treatment option for EDO. Alternative treatment options include endoscopic laser-assisted resection of the ducts, antegrade seminal-vesicle lavage to relieve EDO secondary to inspissated material or calculi, or dilatation of the ejaculatory ducts using 9F seminal vesicoscopy or balloon.

First line fertility treatment strategies regarding IUI and IVF require clinical evidence

Abstract: The advent of intracytoplasmic sperm injection (ICSI) has contributed to a significant growth in the delivery of assisted conception technique, such that IVF/ICSI procedures are now recommended over other interventions. Even the UK National Institute for Health Care Excellence (NICE) guidelines controversially recommends against intrauterine insemination (IUI) procedures in favour of IVF. We reflect on some of the clinical, economic, financial and ethical realities that have been used to selectively promote IVF over IUI, which is less intrusive and more patient friendly, obviates the need for embryo storage and has a global application. The evidence strongly favours IUI over IVF in selected couples and national funding strategies should include IUI treatment options. IUI, practised optimally as a first line treatment in up to six cycles, would also ease the pressures on public funds to allow the provision of up to three IVF cycles for couple who need it. Fertility clinics should also strive towards ISO15189 accreditation standards for basic semen diagnosis for male infertility used to triage ICSI treatment, to reduce the over-diagnosis of severe male factor infertility. Importantly, there is a need to develop global guidelines on inclusion policies for IVF/ICSI procedures. These suggestions are an ethically sound basis for constructing the provision of publicly funded fertility treatments.

Feasibility of performing dynamic sentinel lymph node biopsy as a delayed procedure in penile cancer

Abstract: Patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), normally undergo dynamic sentinel lymph node biopsy (DSNB) at the same time as the primary penile surgery. The aim of this study is to investigate the diagnostic accuracy and clinical outcomes of performing DSNB in patients who have already undergone surgery for the primary penile cancer. Ninety-two patients with unilateral or bilateral impalpable inguinal lymph nodes (LNs) who had already undergone primary resection of the penile tumour (stage ≥ T1G2) were included in this study. All patients underwent a preoperative USS of the groin(s) with fine needle aspiration cytology (FNAC). Provided that the FNAC was clear, DSNB was performed. Radical inguinal lymphadenectomy was performed if the histological analysis of the SLN confirmed the presence of micrometastatic disease. DSNB was undertaken in 165 groins with a nonvisualisation rate of 4.8 % (8/165 groins). The SLN was positive for micrometastatic disease in nine groins (5.5 %) from a total of eight patients (8.7 %). One patient developed regional recurrence in a prepubic LN after excision of bilateral negative SLN (1.1 %). The three-year disease-specific survival for patients with negative and positive SLN was 98.8 and 87.5 %, respectively (p = 0.042). Using DSNB, occult LN metastases in penile cancer can be detected with a sensitivity of 88.9 % and specificity of 100 %. We have demonstrated that DSNB is feasible as a delayed procedure to localise the SLN. Surgical resection of the primary penile lesion does not appear to change the lymphatic drainage.

2016 Laboratory guidelines for postvasectomy semen analysis: Association of Biomedical Andrologists, the British Andrology Society and the British Association of Urological Surgeons

Abstract: Post-vasectomy semen analysis (PVSA) is the procedure used to establish whether sperm are present in the semen following a vasectomy. PVSA is presently carried out by a wide variety of individuals, ranging from doctors and nurses in general practitioner (GP) surgeries to specialist scientists in andrology laboratories, with highly variable results.Key recommendations are that: (1) PVSA should take place a minimum of 12 weeks after surgery and after a minimum of 20 ejaculations. (2) Laboratories should routinely examine samples within 4 h of production if assessing for the presence of sperm. If non-motile sperm are observed, further samples must be examined within 1 h of production. (3) Assessment of a single sample is acceptable to confirm vasectomy success if all recommendations and laboratory methodology are met and no sperm are observed. Clearance can then be given. (4) The level for special clearance should be <100 000/mL non-motile sperm. Special clearance cannot be provided if any motile sperm are observed and should only be given after assessment of two samples in full accordance with the methods contained within these guidelines. Surgeons are responsible both preoperatively and postoperatively for the counselling of patients and their partners regarding complications and the possibility of late recanalisation after clearance. These 2016 guidelines replace the 2002 British Andrology Society (BAS) laboratory guidelines and should be regarded as definitive for the UK in the provision of a quality PVSA service, accredited to ISO 15189:2012, as overseen by the United Kingdom Accreditation Service (UKAS).

Human Papillomavirus Infection and Vaccination in Males.

Abstract: Context Human papillomavirus (HPV) is the commonest sexually transmitted pathogen in humans and is linked to the aetiopathogenesis for both benign and malignant disease in men. Objective To evaluate and summarise the evidence for HPV infection and vaccination in men. Evidence acquisition A search of Medline, PubMed, and Scopus was performed to identify articles published in English within the last 10 yr addressing HPV epidemiology, the natural history of HPV infection and its long-term consequences, and vaccination in men. Relevant studies were then screened, and the data were extracted, analysed, and summarised. The Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria were applied. Evidence synthesis HPV has an overall prevalence of >20% among men, although a minority of individuals develop external genital lesions (EGLs). The risk of acquiring a new HPV infection is robustly linked to sexual behaviour, with the most commonly infected sites being the prepuce, shaft, glans, corona, and scrotum. Of all cancer cases among men, 2% are attributable to HPV, and up to 50% of penile cancers are estimated to be either directly or indirectly driven by it, with HPV-16 the subtype most frequently isolated. Currently there are two different vaccines approved for men, with a good immunogenic profile and efficacy of up to 80% against EGLs; however, efficacy data regarding malignant lesions are still limited. Conclusions HPV, owing to its high prevalence and harmful consequences for men's health, has recently attracted considerable attention. Novel insights into the natural history of HPV infection, together with the successful development of several efficacious vaccines, have provided valuable tools in the prevention of HPV infections and their related consequences. HPV vaccination appears to be the only reliable method to provide protection against new HPV infections in men. Patient summary Human papillomavirus (HPV) infection is very common among sexually active men and can lead to more serious consequences, including cancer. Male vaccination is both a safe and efficacious option preventing both HPV infection and its long-term consequences.

Benign male genital dermatoses

Abstract: Males with genital skin disease may present to clinicians in primary care, dermatology, genitourinary medicine, or urology clinics. Male genital dermatoses encompass a wide variety of skin lesions and rashes, some of which are limited to the genital area whereas others, such as psoriasis, can be part of a more generalised skin disorder. Genital skin disease can impact on the physical, psychological, and sexual wellbeing of men. Some dermatoses are precancerous, and cancer of the penis is associated with morbidity and mortality and litigation.1 This clinical update provides a guide to normal anatomical variations of the penis, how to recognise and manage common benign male genital dermatoses, and when to refer for specialist opinion. #### Sources and selection criteria We searched PubMed and Google Scholar for clinically relevant studies (Jan 2000 to Jul 2016), and the Cochrane Library, using the search terms “Balanitis”, “Balanoposthitis”, “Penile Dermatoses”, “Genital Dermatoses”, along with terms specific to each condition. We consulted the Cochrane Library, National Institute for Health and Care Excellence, British Association of Dermatologists, and British Association for Sexual Health and HIV for guidelines. Patients may be asymptomatic or describe pruritus, soreness, pain, dyspareunia, splitting of the foreskin, non-retractile foreskin (phimosis) or foreskin fixed in retraction (paraphimosis), scaling, erosion, and ulceration.2 3 The foreskin is a delicate tissue that is in close contact with urine, sweat, moisture, sexual secretions, desquamative products, detergents, potential allergens, and microbes. These factors may expose the foreskin to general irritation, pain, and dysfunction (eg, paraphimosis or phimosis, dribbling of urine, dyspareunia).3 4 Further progression of infection and inflammation can cause scarring, disfigurement, and, rarely, precancerous or cancerous lesions. Most men presenting to a specialist male genital dermatology clinic are uncircumcised.5 Circumcision protects men from inflammatory genital dermatoses, including psoriasis, seborrhoeic dermatitis, lichen planus, and lichen sclerosus.5 Predisposition to …

Diagnosis and management of priapism

Abstract: Priapism, a prolonged penile erection, is a rare urological emergency which can pose a significant management challenge. In this article the authors describe the pathophysiology and management of the condition.

Complications of Penile Prosthesis Surgery

Abstract: Complications are not an uncommon occurrence during and after penile prosthesis surgery. Fortunately, if complications are managed promptly according to established principles, the morbidity of the complications can be minimized.

HPV and Penile Cancer: Perspectives on the Future Management of HPV-Positive Disease.

Abstract: Over the past 5 years, several studies have investigated the molecular profiling of penile carcinomas, examining both genomic and epigenetic alterations. These studies have revealed distinct molecular pathways associated with HPV status.

Molecular Biology of Penile Cancer

Abstract: Penile cancer is a rare but potentially mutilating disease in developed countries. The rarity of the disease has presented a significant obstacle to conducting high quality powered research in this area. Nevertheless, steady progress has been made in describing both the depth and breadth of molecular aberrations and drivers of this disease. The majority of studies have used a candidate gene approach focusing on the main oncogenic pathways that exist across all cancers. However, high throughput whole genome approaches are now being utilised to examine the genetic and epigenetic drivers of this disease. It is hoped that these approaches will reveal the next generation of prognostic biomarkers and uncover new therapeutic targets.

Prosthetics and the Prostate

Abstract: The management of bladder outflow obstruction has progressed since the early management using catheters and drainage tubes to empty the bladder. Surgical interventions initially involved open retropubic prostatectomies but with the advancement of endoscopy, a number of techniques to resect the prostate are now common place. This chapter covers prosthetic devices used in the management of bladder outflow obstruction.