Showing papers in "Translational Andrology and Urology in 2017"

From bench to clinic

Abstract: Dr. Ward in his commentary summarized the currently available sperm DNA fragmentation (SDF) tests. He classified the eight SDF assays into four groups based on the different target sites and illustrated the grouping in a diagram to simplify understanding of the readers (1). We would like to supplement, in the following sessions, by (I) further solidifying the current clinical evidence of SDF, and (II) discussing means to move SDF from laboratories to clinics.

Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios.

Abstract: Recent studies show that spermatozoal DNA integrity is essential for normal fertilization and transmission of paternal genetic information to the offspring Additionally, fertilization and embryo development depend on the sperm DNA structure (1,2) Generally, while fertile men have high levels of sperm with intact DNA structure associated with normal semen parameters, infertile men have decreased DNA integrity usually associated with abnormal semen parameters (3,4) However, this association is not unequivocal, as there have been several studies indicating that increased sperm DNA damage can occur in men with conventional sperm parameters within normal reference ranges (3,5,6) Increased sperm DNA damage is defined as the percentage by which the number of cells with defects in protamination of DNA structure in the evaluated sperm cells is calculated and expressed as the sperm DNA fragmentation index (DFI) (3) It is generally accepted that there is a significant negative correlation particularly between the abnormal sperm morphology percentage and DFI (3,6) In the present study, the authors evaluated the diagnostic importance and the clinical significance of sperm DFI tests in infertile males with different clinical conditions (7)

Updates on the epidemiology and risk factors for penile cancer

Abstract: Penile cancer is a rare neoplasm representing less than 1% of all malignancies in the USA and Europe but is a significant public health hazard in the developing world. Male neonatal circumcision has been associated with a dramatic decrease in penile cancer rates with countries such as Israel, where circumcision is widely performed, having the lowest incidence in the world at <0.1% of malignancies. Many risk factors have been identified for penile cancer including phimosis, lack of circumcision, obesity, lichen sclerosis, chronic inflammation, smoking, UVA phototherapy, socioeconomic status, human papillomavirus (HPV) infection and immune compromised states. The relationship between these factors and invasive disease varies and continues to be investigated. Our objective was to present a contemporary overview of the epidemiology and risk factors for invasive penile cancer.

The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility.

Abstract: Sperm DNA fragmentation (SDF) testing has been emerging as a valuable tool for male fertility evaluation. While the essential role of sperm DNA integrity in human reproduction was extensively studied, the clinical indication of SDF testing is less clear. This clinical practice guideline provides recommendations of clinical utility of the test supported by evidence. It is intended to serve as a reference for fertility specialists in identifying the circumstances in which SDF testing should be of greatest clinical value. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. Outcomes of natural pregnancy and assisted reproductive techniques (ART) can be predicted by result of SDF tests. High SDF is also linked with recurrent pregnancy loss (RPL) and failure of ART. Result of SDF testing may change the management decision by selecting the most appropriate ART with the highest success rate for infertile couples. Several studies have demonstrated the benefit in using testicular instead of ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with modifiable lifestyle factor may benefit from SDF testing by reinforcing risk factor modification and monitoring patient’s progress to intervention.

Female genital mutilation/cutting in Africa

Abstract: Female genital mutilation/cutting (FGM/C) is a traditional practice in which the external female genitalia is partially or totally incised or excised for a non-therapeutic reason, usually without the consent of the individual. FGM/C is common in Africa with varying prevalence in different countries, though the incidence is reducing because it is considered a human rights issue with tremendous advocacy for its elimination by mainly nongovernmental organizations. It is mainly underreported in many countries in Africa especially where it has been declared illegal. FGM/C is often performed by a nonmedical practitioner with the aim of fulfilling religious or cultural rites and sometimes for economic benefits with the resultant acute, intermediate and late complications. It is sometimes performed by medical practitioners when it is speciously believed that its medicalization reduces the complications associated with the practice. The sensitivity of FGM/C is amplified when compared to male circumcision and voluntary alterations of the female external genitalia like piercing and tattooing as similar practices. The magnitude of the physical and psychosocial consequences of FGM/C outweighs the presumed benefits of the procedures highlighting the need for improvement of the multiple preventive measures by all the stakeholders and in all the sectors.

Erectile dysfunction in fit and healthy young men: psychological or pathological?

Abstract: Epidemiological studies consistently show that prevalence of erectile dysfunction (ED) increases with ageing. Nonetheless, complaints of ED even in younger men are becoming more and more frequent. Healthcare professionals working in Sexual Medicine but even those operating in different clinical contexts might be adequately prepared to answer this increasing requirement. ED in younger men is likely to be overlooked and dismissed without performing any medical assessment, even the most basic ones, such as collection of medical history and physical exam. This is due to the widespread assumption that ED in younger individuals is a self-limiting condition, which does not deserve any clinical evaluation or therapy and can be managed only with patient reassurance. However, evidence shows that, in younger subjects, organic, psychological and relational conditions can contribute to the pathogenesis of ED and all these conditions might be evaluated and treated, whenever necessary. Among the organic conditions contributing to the onset of ED, metabolic and cardiovascular (CV) risk factors are surprisingly of particular relevance in this age group. In fact, in younger men with ED, even more than in older ones, recognizing CV risk factors or conditions suggestive of cardio-metabolic derangements can help identifying men who, although at low absolute risk due to young age, carry a high relative risk for development of CV events. In this view, the assessment of a possible organic component of ED even in younger individuals acquires a pivotal importance, because it offers the unique opportunity to unearth the presence of CV risk factors, thus allowing effective and high quality preventive interventions.

Genital tuberculosis: current status of diagnosis and management

Abstract: Genitourinary Tuberculosis (GUTB) is the second most common extra-pulmonary manifestation of tuberculosis (Tb) and an isolated involvement of genital organs is reported in 5–30% of the cases. Genital involvement results from primary reactivation of latent bacilli either in the epididymis or the prostate or by secondary spread from the already infected urinary organs. The epididymis are the commonest involved organs affected primarily by a hematogenous mode of spread. Tb is characterized by extensive destruction and fibrosis, thus an early diagnosis may prevent function and organ loss. The gold standard for diagnosis is the isolation and culture of mycobacterium tuberculosis bacilli and in the cases of suspected GUTB, it is commonly looked for in the urinary samples. All body fluid specimens from possible sites of infection and aspirates from nodules must also be subjected to examination. Radiologic investigations including ultrasonography and contrast imaging may provide supportive evidence. Anti-tubercular chemotherapy is the first line of management for all forms of genital Tb and a 6 months course is the standard of care. Most patients with tubercular epididymo-orchitis respond to antitubercular therapy but may require open or percutaneous drainage. Infertility resulting from the tubercular affliction of the genitalia is multifactorial in origin and may persist even after successful chemotherapy. Multiple organ involvement with obstruction at several sites is characteristic and most of these cases are not amenable to surgical reconstruction. Thus, assisted reproduction is usually required. Post treatment, regular annual follow up is recommended even though, with the current multi drug therapy, the chances of relapse are low.

Erectile dysfunction, masculinity, and psychosocial outcomes: a review of the experiences of men after prostate cancer treatment

Abstract: Prostate cancer (PC) treatment side-effects such as erectile dysfunction (ED) can impact men’s quality of life (QoL), psychosocial and psycho-sexual adjustment. Masculinity (i.e., men’s identity or sense of themselves as being a man) may also be linked to how men respond to PC treatment and ED however the exact nature of this link is unclear. This review aims to provide a snapshot of the current state of evidence regarding ED, masculinity and psychosocial impacts after PC treatment. Three databases (Medline/PsycINFO, CINHAL, and EMBASE) were searched January 1st 1980 to January 31st 2016. Study inclusion criteria were: patients treated for PC; ED or sexual function measured; masculinity measured in quantitative studies or emerged as a theme in qualitative studies; included psychosocial or QoL outcome(s); published in English language, peer-reviewed journal articles. Fifty two articles (14 quantitative, 38 qualitative) met review criteria. Studies were predominantly cross-sectional, North American, samples of heterosexual men, with localised PC, and treated with radical prostatectomy. Results show that masculinity framed men’s responses to, and was harmed by their experience with, ED after PC treatment. In qualitative studies, men with ED consistently reported lost (no longer a man) or diminished (less of a man) masculinity, and this was linked to depression, embarrassment, decreased self-worth, and fear of being stigmatised. The correlation between ED and masculinity was similarly supported in quantitative studies. In two studies, masculinity was also a moderator of poorer QoL and mental health outcomes for PC patients with ED. In qualitative studies, masculinity underpinned how men interpreted and adjusted to their experience. Men used traditional (hegemonic) coping responses including emotional restraint, stoicism, acceptance, optimism, and humour or rationalised their experience relative to their age (ED inevitable), prolonged life (ED small price to pay), definition of sex (more than erection and penetration), other evidence of virility (already had children) or sexual prowess (sown a lot of wild oats). Limitations of studies reviewed included: poorly developed theoretical and context-specific measurement approaches; few quantitative empirical or prospective studies; moderating or mediating factors rarely assessed; heterogeneity (demographics, sexual orientation, treatment type) rarely considered. Clinicians and health practitioners can help PC patients with ED to broaden their perceptions of sexual relationships and assist them to make meaning out of their experience in ways that decrease the threat to their masculinity. The challenge going forward is to better unpack the relationship between ED and masculinity for PC patients by addressing the methodological limitations outlined so that interventions for ED that incorporate masculinity in a holistic way can be developed.

Relationship between human papillomavirus and penile cancer-implications for prevention and treatment.

Abstract: Penile cancer is a rare disease in the United States, but rates are increasing, causing concern. Several risk factors have been associated with the disease, including human papillomavirus (HPV) infection. Knowledge of HPV pathogenesis has led to the development of a vaccine, which has proven instrumental in reducing the incidence of female HPV-related cancers, but results in men have yet to be elucidated. Fortunately, rates of vaccination are up-trending in both males and females in the past several years. In addition, targeted therapies are the focus of several ongoing research efforts. Some of these therapeutics are currently in use, while several are in trials. With continued patient education and research, both treatment and prevention of HPV-related pre-malignant lesions and penile cancer will likely diminish.

Microdissection Testicular Sperm Extraction

Abstract: Microdissection testicular sperm extraction (microTESE) is considered the gold standard method for surgical sperm retrieval among patients with non-obstructive azoospermia (NOA). In this review, we will discuss the optimal evaluation of NOA patients and strategies to medically optimize NOA patients prior to microTESE. In addition, we will also discuss technical principles and pearls to maximize the chances of successful sperm retrieval, sperm retrieval rates (SRR) based upon testicular histology, predictors of successful sperm retrieval, gonadal recovery following microTESE, and potential complications.

Aging related erectile dysfunction-potential mechanism to halt or delay its onset.

Abstract: Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one’s genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40’s, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient’s age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from “leaking” out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with essential hypertension.

Degree of twisting and duration of symptoms are prognostic factors of testis salvage during episodes of testicular torsion

Abstract: Background: Testicular torsion is surgical emergency. Prompt diagnosis and treatment of testicular torsion is essential for testicular viability. At surgical exploration, the spermatic cord is seen twisted a variable number of times around its longitudinal axis. There is scant data regarding the degree of twisting and its association with testis outcomes. The purpose of our study is to explore how the degree of torsion factors into testicular outcome using follow-up data. Methods: We retrospectively reviewed the records of adolescent males who presented with testicular torsion to our institution, looking at duration of pain symptoms, degree of torsion documented in the operative note, procedure performed (orchiopexy versus orchiectomy), and follow-up clinic data for whether testicular atrophy after orchiopexy was present. A non-salvageable testis was defined as orchiectomy or atrophy. Receiver operator characteristics (ROC), multivariate, and logistic regression analyses were performed to determine the probability of a non-salvageable torsed testis based on time and degree of twisting. Results: Eighty-one patients met our study criteria, with 55 testes deemed viable and 26 non-salvageable. We found a 25.7% atrophy rate after orchiopexy. Cut-off values of 8.5 h and 495 degrees of torsion would provide sensitivities of 73% and 53%, respectively, with specificity of 80% for both. Only duration and age were correlated with the risk of non-salvage on multivariate analysis. Logistic regression generated linear probability formulas of 4 + (3 × hours) and 7 + (0.05 × degrees) in calculating the probability of non-salvage with strong correlation. Conclusions: We were able to derive separate formulas to determine the viability of the torsed testis based on symptom duration and degrees of twisting. Fifteen h of symptoms and 860 degrees of torsion gives testes a 50% salvage rate. Interestingly, we also found that about 1 out of every 4 testes undergoes atrophy after orchiopexy.

DNA damage in human spermatozoa; important contributor to mutagenesis in the offspring.

Abstract: The importance of sperm DNA damage on human reproduction is increasingly be recognized. Chromatin compaction does not only affect fertility but also exert significant implication of the health and wellbeing of the offspring. Two-step hypothesis has been proposed and represents a rational explanation of how sperm DNA damage occurs. Generation of vulnerable spermatozoa as a result of defect during spermatogenesis represents the first stage of sperm DNA damage. It is followed by oxidative attack which may occurs at all stages of sperm production or transportation due to various causes. As a result, reactive oxygen species constitute a major role in the aetiology of sperm DNA damage. Formation of oxidative base adducts such as 8-hydroxy-2’-deoxyguanosine (8OHdG) commonly occurs upon oxidative attack on sperm DNA. The assessment of oxidative base adducts, therefore, represents another measure of sperm DNA damage. 8OHdG assay may have the advantage in better prediction of offspring health since 8OHdG residues are highly mutagenic. The understanding of sperm DNA damage opens a new doorway to unveil the mystery of human reproduction. On the other hand, there are still many unknowns awaiting for further research. One of the missing link is the relationship between sperm DNA damage and the mutational/epimutational load subsequently carried by the offspring. The demonstration of a positive relationship will further expanding the clinical application of sperm DNA testing and may promote routine use of the test in assessment of male infertility.

A critical comparison of techniques for MRI-targeted biopsy of the prostate

Abstract: MRI-targeted biopsy is a promising technique that offers an improved detection of clinically significant prostate cancer over standard non-targeted biopsy. It is established that prostate MRI is of use in both the primary and repeat biopsy setting for the detection of significant prostate cancer. There are three approaches to targeting biopsies to areas of interest seen on prostate MRI. They each rely on the acquisition and reporting of a diagnostic quality multi-parametric MRI scan used to identify areas of interest, and the subsequent use of those diagnostic quality images in combination with real-time images of the prostate during the biopsy procedure. The three techniques are: visual registration of the MRI images with a real-time ultrasound image; software-assisted fusion of the MRI images and the real-time ultrasound images, and in-bore biopsy, which requires registration of a diagnostic quality MRI scan with a real time interventional MRI image. In this paper we compare the three techniques and evaluate those studies where there is a direct comparison of more than one MRI-targeting technique. PubMed was searched from inception to November 2016 using the search terms (cognitive registration OR visual registration OR fusion biopsy OR in-bore biopsy OR targeted biopsy) AND (prostate cancer OR prostate adenocarcinoma OR prostate carcinoma OR prostatic carcinoma OR prostatic adenocarcinoma) AND (MRI OR NMR OR magnetic resonance imaging OR mpMRI OR multiparametric MRI). The initial search included 731 abstracts. Eleven full text papers directly compared two or more techniques of MRI-targeting, and were selected for inclusion. The detection of clinically significant prostate cancer varied from 0% to 93.3% for visual registration, 23.2% to 100% for software-assisted registration and 29% to 80% for in-bore biopsy. Detection rates for clinically significant cancer are dependent on the prevalence of cancer within the population biopsied, which in turn is determined by the selection criteria [biopsy naive, previous negative biopsy, prostate specific antigen (PSA) selection criteria, presence of a lesion on MRI]. Cancer detection rates varied more between study populations than between biopsy approaches. Currently there is no consensus on which type of MRI-targeted biopsy performs better in a given setting. Although there have been studies supporting each of the three techniques, substantial differences in methodology and reporting the findings make it difficult to reliably compare their outcomes.

Erectile dysfunction, metabolic syndrome, and cardiovascular risks: facts and controversies.

Abstract: Erectile dysfunction (ED) is the most common male sexual dysfunction, and shares many risk factors with systemic conditions including cardiovascular disease (CVD) and the metabolic syndrome (MetS). ED is considered to be an independent risk factor for CVD and can be a harbinger of future cardiovascular events. Given this relationship, each encounter for ED should be viewed by healthcare providers as an opportunity to screen for CVD and other comorbid conditions, including the MetS, that can significantly affect a man's overall health. While universally accepted screening guidelines are lacking, expert panels do recommend an approach to risk stratification in men with ED. In this review, we discuss the current state of understanding of the relationship between ED, the MetS, and CV risk, and how this impacts the approach to the patient presenting with ED.

Penile prosthesis implant: scientific advances and technological innovations over the last four decades.

Abstract: Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis. IPP is considered a superior option to malleable prosthesis as it produces penile rigidity and flaccidity that closely replicates a normal penile erectile function. Since the introduction of IPP by Scott in 1973, surgical landscape for penile prosthesis implantation has changed dramatically. Advances in prosthesis design, device technologies and surgical techniques have made penile prosthesis implant a more natural, durable and reliable device. The following article reviews the scientific advances and technological innovation in modern penile prosthesis implants over the last four decades.

Sperm DNA fragmentation testing: a cross sectional survey on current practices of fertility specialists

Abstract: Background: Sperm DNA fragmentation (SDF) testing has been recognized as a valuable tool in the evaluation of infertile men. Despite that, its routine use in clinical practice is still hampered by the lack of understanding of the specific clinical scenarios where SDF testing is most beneficial. The aim of this study was to investigate fertility specialists evaluation of infertility of SDF testing in the context of male infertility evaluation and assisted reproductive technology. Methods: A questionnaire was developed to survey the major aspects of SDF testing and was mailed to specialists with demonstrated clinical experience in the field of infertility. A total of 65 professionals were invited to answer issues related to the utility of SDF testing, the testing methods they used, were the SDF cut-off values, and the cost of testing and the perceived drawbacks of the test results. Specific clinical scenarios were presented to assess whether or not participants would recommend SDF testing. The frequency of responses was analyzed. Results: Forty-nine participants from 19 countries responded to the study questionnaire. SDF testing was commonly ordered by 39 (79.6%) respondents; while 10 (20.4%) did not order SDF testing during fertility evaluation. Terminal deoxynucleotidyl transferase nick end labelling (TUNEL) and sperm chromatin structure assay (SCSA) were most commonly utilized (30.6% for both), followed by sperm chromatin dispersion (SCD) (20.4%), single cell gel electrophoresis (Comet) (6.1%) and other methods (12.2%). SDF was most commonly requested in couples presenting with recurrent conventional in vitro fertilization (IVF) failure or pregnancy loss following conventional IVF (91.8%), followed by couples with recurrent first trimester natural pregnancy loss (NPL) and recurrent pregnancy loss (RPL) following intracytoplasmic sperm injection (ICSI) (85.7% for both). A 67.3% of respondents admitted that an SDF test result would affect their decision to utilize testicular instead of ejaculated sperm for ICSI. The reported mean ± standard deviation (SD) cost (USD) of SDF testing was 170.4±122.9. Cost (46.9%), poor validation (36.7%) and low precision (18.3%) were the most commonly reported drawbacks of SDF testing. Conclusions: SDF testing is utilized in the evaluation of infertility patients by a majority of fertility specialists under specific clinical scenarios. Shortcomings, such as the presence of several SDF testing methods with different cut-off values and the test charges were some of the reasons hampering the routine use of SDF in the evaluation of infertile men.

Guidelines of guidelines: a review of urethral stricture evaluation, management, and follow-up.

Abstract: Background: Our objective is to report a comparative review of recently released guidelines for the evaluation, management, and follow-up of urethral stricture disease. Methods: This is an analysis of the American Urologic Association (AUA) and Societe Internationale d’Urologie (SIU) guidelines on urethral stricture. Strength of recommendations is stratified according to letter grade that corresponds to the level of evidence provided by the literature. Results: Although few, the discrepancies between the recommendations offered by the two guidelines can be best explained by varying interpretations of the literature and available evidence on urethral strictures. When comparing the AUA guidelines and the SIU guidelines on urethral stricture, there are very few discrepancies. Perhaps the most notable difference is in the use of repeat DVIU or urethral dilation after an initial failed attempt. SIU guidelines state that there are instances where repeat DVIU or urethral dilation can be indicated, and they give a range of time at which stricture recurrence post procedure mandates an urethroplasty (less than 3 to 6 months). The AUA guidelines definitively state that repeat endoscopic procedures should not be offered as an alternative to urethroplasty, and they do not mention time of stricture recurrence as a factor. SIU guidelines allow for management of urethral stricture with indwelling urethral stenting. Conclusions: Overall there is a need for more high quality research in the work up, management, and follow up care of urethral stricture.

Complications: acknowledging, managing, and coping with human error.

Abstract: Errors are inherent in medicine due to the imperfectness of human nature. Health care providers may have a difficult time accepting their fallibility, acknowledging mistakes, and disclosing errors. Fear of litigation, shame, blame, and concern about reputation are just some of the barriers preventing physicians from being more candid with their patients, despite the supporting body of evidence that patients cite poor communication and lack of transparency as primary drivers to file a lawsuit in the wake of a medical complication. Proper error disclosure includes a timely explanation of what happened, who was involved, why the error occurred, and how it will be prevented in the future. Medical mistakes afford the opportunity for individuals and institutions to be candid about their weaknesses while improving patient care processes. When a physician takes the Hippocratic Oath they take on a tremendous sense of responsibility for the care of their patients, and often bear the burden of their mistakes in isolation. Physicians may struggle with guilt, shame, and a crisis of confidence, which may thwart efforts to identify areas for improvement that can lead to meaningful change. Coping strategies for providers include discussing the event with others, seeking professional counseling, and implementing quality improvement projects. Physicians and health care organizations need to find adaptive ways to deal with complications that will benefit patients, providers, and their institutions.

The dangers of sexual enhancement supplements and counterfeit drugs to “treat” erectile dysfunction

Abstract: Counterfeit phosphodiesterase-5 inhibitors (PDE-5i) are an increasing problem. Already in widespread use, the market for PDE-5i is steadily growing as the population ages. Counterfeiters are taking advantage of this growing market by developing illicit and counterfeit PDE-5i products. Many factors are contributing to the rapid growth of the illicit market, such as the low risk of prosecution, potentially high financial reward, and ease of distribution via Internet pharmacies. Consumers of illicit PDE-5i often do not realize they are using counterfeit products and placing themselves at an unnecessary health risk. Others seek to bypass the legitimate healthcare system due to either embarrassment of the underlying condition or desire for cheaper alternatives. However, taking illicit PDE-5i may harm consumers directly, as many illicit products contain detrimental contaminants and inaccurate amounts of the active ingredient without the appropriate warnings. Bypassing the legitimate healthcare system also endangers consumers indirectly, as erectile dysfunction (ED) is often associated with other medical comorbidities that patients should be screened for. Furthermore, PDE-5i can have potentially dangerous interactions with other pharmaceuticals that are rarely warned against with counterfeit PDE-5i. This communication reviews the literature regarding counterfeit PDE-5i, and summarizes both the scope and dangers of the illicit PDE-5i market.

The penoscrotal surgical approach for inflatable penile prosthesis placement

Abstract: Optimizing outcomes with placement of inflatable penile prostheses (IPPs) can be challenging, especially in inexperienced hands. In this article, we outline Dr. Kohler's penoscrotal penile prosthesis surgical approach. We also highlight patient selection, post-operative care and complications.

Buccal mucosal graft urethroplasty in men-risk factors for recurrence and complications: a third referral centre experience in anterior urethroplasty using buccal mucosal graft.

Abstract: Background: Urethral stricture disease is a challenging condition to treat and several approaches including direct visual internal urethrotomy (DVIU) and anastomotic or augmentation urethroplasties based on the use of flaps and graft have been reported. The aim of this study is to determine risk factors for stricture recurrence and complications in patients having buccal mucosal graft (BMG) urethroplasty for anterior urethral stricture under a single surgeon in a third referral centre in UK. Methods: We conducted a retrospective review of a prospectively gathered database of 128 patients having various forms of BMG urethroplasty between 2001 and 2015. Success and failure in terms of stricture recurrence, patient demographics, stricture aetiology and anatomy, and the adverse outcomes of: post-micturition dribbling (PMD), erectile dysfunction (ED) >12 months and complications were recorded in order to determine risk factors for recurrent stricture and complications. Results: The mean age of all patients was 42.8 years (range, 16–74 years). Average follow-up was 45 months (range, 3–159 months). The total re-stricture rate was 19% (24 men). PMD was reported in 16% (n=20) and ED in 12.5% (n=16). All ED was none organic and responded to oral PDE5 inhibitor treatment. Post-operative complications were reported in 16 patients (12.5%). The most frequent complications recorded were urinary fistula (n=4; 3.1%), graft contracture (n=4; 3.1%) and graft failure (n=4; 3.1%), all reported after penile urethroplasty. Univariate analysis indicated that age at surgery, stricture length, site and aetiology were all significant risk factors for stricture recurrence. On multivariate analysis penile site was the only significant independent variable for restricture. Conclusions: BMG urethroplasty represents a reliable therapeutic option for patient with urethral strictures with a success rate of 81% at 45 months of follow-up. Complications are more common in complex stricture of the penile urethra. On multivariate analysis penile site was the only significant independent variable for re-stricture.

Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

Abstract: For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs . low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs . low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other studies showed a significant increased-risk of PCa. Remaining studies reported null-risks values. Second part: eight of out of 25 studies reported an increased-risk of PCa for men with high levels of testosterone compared to low, but only four were statistically significant. However, 17 studies showed a decreased-risk of PCa after comparing high vs . low levels of testosterone, but 11 studies/analyses were statistically significant. Third part: two meta-analyses of randomized placebo-controlled trials (n=8 and n=11, each) that investigated use of TTh with PCa reported not significant decreased-risks of PCa. The contention that high levels of testosterone or that the use of TTh increases the risk of PCa doesn’t seem to be supported from the literature. Yet, we still need a study with the adequate power, follow-up data, epidemiological, pathological and clinical data that can support the safety and beneficial effects of high levels of endogenous testosterone or use of TTh in the natural history of PCa and in men’s health.

Reactive oxygen species and sperm DNA fragmentation.

Abstract: Dr. Dada demonstrated her extensive knowledge about sperm DNA fragmentation (SDF) in her elegantly written commentary with a comprehensive discussion on issues such as genetic health of offspring, value of SDF testing in lifestyle factors, modification of SDF by oocyte, role of sperm preparation, concept of reductive stress, methodology of SDF testing, and use of antioxidant and testicular sperm (1). In our response, we have elaborated on the association between reactive oxygen species (ROS) and SDF which has been mentioned repeatedly in Dr. Dada's commentary.

Evaluation of sperm chromatin structure and DNA strand breaks is an important part of clinical male fertility assessment.

Abstract: As reviewed by Agarwal et al. (1) and recently stated by Vu Bach and Schlegel (2), “numerous studies have attempted to assess the association between elevated sperm DNA fragmentation (SDF) and ART outcomes. Unfortunately, variations between SDF assays, protocols, and thresholds and differences in study populations have resulted in systematic reviews and meta-analyses fraught with heterogeneity and unable to come to robust conclusions”. However, these early meta-analyses were considered a near impossible task leading to vague and questionable conclusions. Recent studies have refined protocols for the Sperm Chromatin Structure Assay (SCSA) (3,4) TUNEL (5), SCD (6) and COMET (7) tests. A major consideration for standardizing a protocol is to identify the SDF thresholds. While this has often been described as a single% SDF, e.g., 30% listed as the SCSA threshold in Agarwal et al. (1), more recent SCSA studies have listed two or three thresholds depending on the method of fertilization (see below).

Prevention, identification, and management of post-operative penile implant complications of infection, hematoma, and device malfunction.

Abstract: Penile prosthesis implant surgery is an effective management approach for a number of urological conditions, including medication refractory erectile dysfunction (ED). Complications encountered post-operatively include infection, bleeding/hematoma, and device malfunction. Since the 1970s, modifications to these devices have reduced complication rates through improvement in antisepsis and design using antibiotic coatings, kink-resistant tubing, lock-out valves to prevent autoinflation, and modified reservoir shapes. Device survival and complication rates have been investigated predominately by retrospective database-derived studies. This review article focuses on the identification and management of post-operative complications following penile prosthetic and implant surgery. Etiology for ED, surgical technique, and prosthesis type are variable among studies. The most common post-operative complications of infection, bleeding, and device malfunction may be minimized by adherence to consistent technique and standard protocol. Novel antibiotic coatings and standard antibiotic regimen may reduce infection rates. Meticulous hemostasis and intraoperative testing of devices may further reduce need for revision surgery. Additional prospective studies with consistent reporting of outcomes and comparison of surgical approach and prosthesis type in patients with variable ED etiology would be beneficial.

A review of varicocele repair for pain

Abstract: A dilation of the pampiniform venous plexus in the scrotum above the testicle, called a varicocele, affects approximately 15% of the general male population. While the majority is asymptomatic, pain results in up to 10% of cases of varicoceles. The pain associated with varicoceles is typically mild and is described as heavy, achy, or dull—and is usually isolated to the testicle or spermatic cord. Guidelines clearly recommend varicocele repair in males with varicoceles, infertility, and an abnormal semen analysis. While chronic, severe pain is an additional indication for repair, a careful evaluation to rule out other etiologies in addition to a period of conservative management are necessary prior to surgical treatment because of the high incidental prevalence of varicoceles in the general population. Several techniques for varicocele repair have been described, including retroperitoneal, laparoscopic, inguinal, and subinguinal. Additionally, recent adjuncts to improve visualization and identification of critical structures including the operating microscope and microvascular Doppler ultrasound have improved success and complication rates. With careful patient selection, outcomes of varicocele repair with regard to pain are excellent, with over 90% of patients experiencing symptomatic relief. After failure of conservative treatments, a varicocele associated with pain should be considered for repair, and the microsurgical subinguinal approach is the gold standard surgical treatment, offering excellent outcomes while minimizing risk of complications.

Preoperative counseling and expectation management for inflatable penile prosthesis implantation.

Abstract: The inflatable penile prosthesis (IPP) is the gold standard surgical treatment for medical refractory erectile dysfunction (ED). While the modern IPP has enjoyed high satisfaction rates as a product of its continued innovation, reliability, and performance, patient dissatisfaction can still occur. IPP implantation restores physiologic function with cosmetic and psychological consequences, both of which place inherent emphasis on preoperative counseling and expectation management. This review aims to highlight the complex nature of such counseling and provide practitioners with a roadmap to navigate the landscape. Preoperative counseling begins with appropriate patient selection and identification of those patients who are at risk for dissatisfaction as a result of personality characteristics. The informed consent provides a natural framework to discuss the host of complications and risks that are associated with surgery, including infection, device malfunction, damage to nearby structures, and device erosion. Device selection is a nuanced process that merges patient preference with clinical factors and consideration. We address device selection through a description of cylinder construction, pump design, and reservoir placement in the context of preoperative counseling. Lastly, we draw attention to expectation management with a specific focus on possible post-operative changes to penile length and sensation as well as partner involvement. The modern IPP provides excellent results with high patient and partner satisfaction. Ultimately, satisfaction is dependent on multiple factors, but providing accurate, realistic counseling and expectation management prepares patients for the best possible outcomes.

Positron emission tomography (PET) in primary prostate cancer staging and risk assessment

Abstract: Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa. However, some PET agents have shown remarkable promise in staging high-risk PCa (defined as any combination of a clinical T3, a PSA score >20 ng/mL, or a Gleason score of 8-10), as well as biochemical relapse after definitive therapy and metastatic PCa. PET agents can be divided into those that interrogate tumor metabolism (18F-FDG, 11C-Choline, 18F-Choline, 11C-Acetate, 18F-FACBC), hormone receptors (18F-FDHT), and other targets such as prostate specific membrane antigen (PSMA) (68Ga-PSMA, 18F-DCFBC, 18F-DCFPyl) or gastric releasing peptide (18F-GRP or 18F-Bombesin). In this review, we compare the available PCa targeted PET tracers utilized in staging of high risk tumors.

Antioxidants for elevated sperm DNA fragmentation: a mini review

Abstract: We would like to thank Dr. Cho for his insightful commentary on our article discussing the utility of sperm DNA fragmentation (SDF) testing for fertility evaluation (1). The author elegantly summarized the principle concepts of the article and provided his expert views of the topic. Dr. Cho rightly commented that “One of the major huddles of clinical application of a test lies in the lack of treatment modalities. And the development of treatment strategies, e.g., the use of antioxidants and sperm selection methods, must go hand in hand with advancement of sperm DNA testing which was also included in the guideline.” We certainly agree with his view on this point, especially since SDF testing has been criticized based on the unavailability of effective treatment modalities. In reply, we would like to highlight the existing available evidence on antioxidant use in patients with high SDF.