Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Urethral Prolapse Case Report: Surgical and Social Considerations in Senegal.

We present three cases of urethral prolapse in prepubertal females in Senegal who presented with vulvar bleeding. Careful gynecologic and urologic physical exams were performed and revealed urethral origin and prolapse. Conservative versus surgical approaches were taken in different patients, but ultimately, each patient received a urethral meatoplasty. Surgical excision of these masses yielded a full recovery in the patients. A careful review of the literature was then undertaken and showed that surgical excision or ligation of the prolapse is preferable to more conservative treatment. The case series article discusses the rare occurrence of urethral prolapse, as well as the epidemiology and prognostic and therapeutic implications of urethral prolapse in prepubertal females. Introduction. Urethral prolapse is a rare condition occurring mostly in young black females. It can be worrying to the parents as it often causes vulvar bleeding. Case Presentation. We present three cases of urethral prolapse in prepubertal females who presented with vulvar bleeding. Physical exams were performed and revealed urethral origin and prolapse. Each patient underwent a urethral meatoplasty and subsequently experienced a full recovery after respective follow-up of 2 years, 1 year, and 1 year. Conclusion. Urethral prolapse is a rare condition which can be managed successfully by surgery. Plain Language Summary. This case report on pediatric urethral prolapse showcases the different presentations and modalities of treatment, as the literature does not show that a specific treatment is always undertaken. In some countries, there are strong social considerations and they demonstrate difficulty separating sexual abuse from genitourinary pathologies, which are important to address in the treatment of these conditions.

Epidemiological and Diagnostic Aspects of Bladder Bilharziomas in the Urology Department of Idrissa Pouye General Hospital (HOGIP).

Objective: The aim of our study is to assess the diagnostic aspects of bladder bilharzioma in the Urology Department of Idrissa Pouye General Hospital (Senegal). Materials and Methods: It is a descriptive study from January 2013 to December 2018. The patients included in the study were those who had anatomopathological examination of bladder biopsy that showed a schistosomiasis pseudotumor of the bladder. The variables studied were sociodemographic, clinical symptoms, imaging findings, histology, and treatment. The data have been saved and analyzed by the 2013 Excel software. Results: Thirteen patients were included in our study. The average age was 27 ± 12.1 years. Sex ratio was 1.6. The majority of the patients were from the northern part of Senegal. Hematuria was the main symptom for all the patients. Cystoscopy was performed for all the patients and showed 5 granulomas and 8 fibrocalcic polyps. A transurethral resection of the bladder was performed, and treatment with praziquantel (40 mg/kg of bodyweight) has been carried out. One patient presented precancerous lesions such as metaplasia and dysplasia of the bladder mucosa. After a median follow-up of 40 months (6-57 months), ten patients had a favorable clinical and endoscopic outcome. Conclusion: Granulomas and fibrocalcic polyps of the bladder mucosa are, respectively, confused with squamous cell carcinoma and bladder lithiasis in endemic areas of schistosomiasis. Good cystoscopy interpretation can provide the diagnosis of bladder bilharzioma and start the treatment.

Surgical Management of Urolithiasis of the Upper Tract - Current Trend of Endourology in Africa.

Urolithiasis is a global pathology with increasing prevalence rate. The lifetime recurrence of urolithiasis ranges from 10-75% creating a public health crisis in affected regions. The epidemiology of urolithiasis in most parts of Africa and Asia remains poorly documented as incidence and prevalence rates in these settings are extrapolated from hospital admissions. The surgical management of kidney and ureteral stones is based on the stone location, size, the patient's preference and the institutional capacity. To date, the available modalities in the management of urolithiasis includes external shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopy (URS) including flexible and semirigid ureteroscopy. However, regarding the lack of endourological equipment and expertise in most parts of Sub-Saharan Africa (SSA), most urological centers in these regions still consider open surgery for kidney and ureteral stones. This review explores the current trend and surgical management of upper tract urolithiasis in SSA with insight on the available clinical guidelines.

Is Schistosomiasis a Risk Factor for Bladder Cancer? Evidence-Based Facts.

Background . Globally, approximately 20% of malignancy are caused by infection. Schistosoma infection is a major cause of bladder in most part of Africa. In 2018 alone, there were approximately 549,393 new cases and 199,922 deaths from bladder cancer. The presence of Schistosoma ova in the venous plexus of the bladder induces a cascade of inflammation causing significant tissue damage and granulomatous changes. Methodology. A literature review was conducted from 1995 to 2019 using PubMed, Google Scholar, African Journal Online, and Google databases. Relevant data on the association of "Schistosomiasis and Bladder cancer" in sub-Saharan Africa (SSA) were retrieved. Evidence Synthesis. Results from research using animal models to establish the carcinogenesis of Schistosoma and bladder cancer have been helpful but inconclusive. Immunoregulatory cytokines and genetic marker have been identified to play a role in the pathogenesis. In some parts of sub-Saharan Africa, there has been close association of squamous cell carcinoma and histological evidence of Schistosoma ova. Conclusion. There are some data to support the association between schistosomiasis and bladder cancer in sub-Saharan Africa. However, these have been limited by their design and may not sufficiently establish carcinogenesis. There is a need for more genomic and molecular research to better characterize S. haematobium and its effects on the bladder. Such goal will contribute immensely to Schistosoma bladder cancer prevention and control.

Review of Testicular Tumor: Diagnostic Approach and Management Outcome in Africa.

Testicular cancer is a common malignancy in young males with higher incidence in developed nations but with the lowest incidence in Africa (0.3-0.6/100 000). Ironically, the global testicular cancer mortality rate has shown a reverse trend to its incidence with higher rates in low- and middle-income countries (0.5 per 100 000) than in high-income countries. Data from GLOBOCAN 2008 have shown relatively high mortality rates in sub-Saharan countries like Mali, Ethiopia, Niger and Malawi. The prognosis of testicular tumor is good with remarkable chemosensitivity to cisplatin-based regimen. Early diagnosis, careful staging and a multidisciplinary management approach is crucial to achieve this optimal result. These results are achievable in the sub-Saharan region if the relevant resources are appropriated for cancer care and clinical guidelines are formulated in a regional context.

Forecasting Limited Access to Urology in Rural Communities: Analysis of the American Urological Association Census.

OBJECTIVE: To assess an aging subspecialty workforce and growing population that portends challenges in meeting patient care needs. We hypothesized that rural physicians are retiring at higher rates than their urban counterparts in the United States and that this represents a bellwether for workforce challenges at large. METHODS: We analyzed data from the 2014-2016 American Urological Association Census, a sample-weighted representative survey of urologists, as a case study for subspecialists. We compared urologists who work in rural regions to nonrural regions on available characteristics. RESULTS: In 2016, rural urologists accounted for 2.4% of 12,186 practicing urologists in the United States. General urology remained the focus of 90% of rural urologists, compared to 59% of nonrural urologists (P = .03). Alarmingly, 48% of rural physicians were >65 years old in 2016 compared to 29% in 2014, and 33% of rural urologists were solo practitioners compared to 9% of nonrural urologists (P < .01). The planned retirement age for rural physicians increased from 68 in 2014 to 73 in 2016 (P trend = .02). The percentage of rural practice urologists has remained stable since 2014. CONCLUSIONS: Rural urologists are older and provide more general urological care than their nonrural counterparts. Rural urologists are postponing retirement. Although this might be due to personal desires and financial goals, it may also be due to a relative absence of potential junior partners. Given that almost 50% of rural urologists were older than 65 in 2016, this is not a sustainable solution to an impending shortage of physicians. Greater innovation in telemedicine or alternative care models will soon be needed.

Management of Renal Cell Carcinoma-Current Practice in Sub-Saharan Africa.

There is a global variation in the incidence of renal masses with the developed nations having a greater incidence. About 80-90% of renal malignancies are renal cell carcinomas (RCC) which account for 2-4% of all cancers. In Africa and the Middle East, the age-standardized incidence for RCC is 1.8-4.8/100,000 for males and 1.2-2.2/100,000 for females. The management of renal cell cancer is challenging. A multidisciplinary approach is effective for diagnosis, staging, and treatment. Guidelines recommend active surveillance, thermal ablation, partial nephrectomy, radical nephrectomy, cytoreductive nephrectomy and immunotherapy as various modalities for various stages of RCC. However, open radical nephrectomy is most widely adopted as an option for treatment at various stages of the disease in sub-Saharan Africa due to its cost-effectiveness, applicability at various stages, and the reduced cost of follow-up. Nevertheless, most patients in the region present with the disease in the advanced stage and despite surgery the prognosis is poor.

Management of Advanced and Metastatic Prostate Cancer: A Need for a Sub-Saharan Guideline.

The estimated incidence rate of prostate cancer in Africa was 22.0/100,000 in 2016. The International Agency for Research on Cancer (IARC) has cited prostate cancer as a growing health threat in Africa with approximated 28,006 deaths in 2010 and estimated 57,048 deaths in 2030. The exact incidence of advanced and metastatic prostate cancer is not known in sub-Saharan Africa. Hospital-based reports from the region have shown a rising trend with most patients presenting with advanced or metastatic disease. The management of advanced and metastatic prostate cancer is challenging. The available international guidelines may not be cost-effective for an African population. The most efficient approach in the region has been surgical castration by bilateral orchidectomy or pulpectomy. Medical androgen deprivation therapy is expensive and may not be available. Patients with metastatic castrate-resistant prostate cancer tend to be palliated due to the absence or cost of chemotherapy or second-line androgen deprivation therapy in most of Africa. A cost-effective guideline for developing nations to address the rising burden of advanced prostate cancer is warranted at this moment.

Perspectives From Authors and Editors in the Biomedical Disciplines on Predatory Journals: Survey Study.

BACKGROUND: Predatory journals fail to fulfill the tenets of biomedical publication: peer review, circulation, and access in perpetuity. Despite increasing attention in the lay and scientific press, no studies have directly assessed the perceptions of the authors or editors involved. OBJECTIVE: Our objective was to understand the motivation of authors in sending their work to potentially predatory journals. Moreover, we aimed to understand the perspective of journal editors at journals cited as potentially predatory. METHODS: Potential online predatory journals were randomly selected among 350 publishers and their 2204 biomedical journals. Author and editor email information was valid for 2227 total potential participants. A survey for authors and editors was created in an iterative fashion and distributed. Surveys assessed attitudes and knowledge about predatory publishing. Narrative comments were invited. RESULTS: A total of 249 complete survey responses were analyzed. A total of 40% of editors (17/43) surveyed were not aware that they were listed as an editor for the particular journal in question. A total of 21.8% of authors (45/206) confirmed a lack of peer review. Whereas 77% (33/43) of all surveyed editors were at least somewhat familiar with predatory journals, only 33.0% of authors (68/206) were somewhat familiar with them (P<.001). Only 26.2% of authors (54/206) were aware of Beall's list of predatory journals versus 49% (21/43) of editors (P<.001). A total of 30.1% of authors (62/206) believed their publication was published in a predatory journal. After defining predatory publishing, 87.9% of authors (181/206) surveyed would not publish in the same journal in the future. CONCLUSIONS: Authors publishing in suspected predatory journals are alarmingly uninformed in terms of predatory journal quality and practices. Editors' increased familiarity with predatory publishing did little to prevent their unwitting listing as editors. Some suspected predatory journals did provide services akin to open access publication. Education, research mentorship, and a realignment of research incentives may decrease the impact of predatory publishing.

Qualitative Analysis of the Content Found in Online Discussion Boards for Urethral Stricture Disease and Urethroplasty.

OBJECTIVE: To describe the patient experience and chief concerns with urethroplasty to improve physician understanding and patient education. Online discussion boards allow patients with urethral stricture disease (USD) to connect with other USD patients. It is unknown how men use these web resources and what information is available about urethroplasty. METHODS: Three online forums featuring urethroplasty were identified by Google search. Thematic analysis categorized the content of posts using manually applied codes, with inter-rater reliability and descriptive statistics generated by Dedoose (Los Angeles, CA). RESULTS: A total of 140 unique posters contributed 553 posts to the forums. Posts were categorized as information support (n = 651), issues posturethroplasty (n = 470), own experience preurethroplasty (n = 336), feelings towards other posters (n = 312), what to expect posturethroplasty (n = 265), feelings after urethroplasty (n = 228), and considerations before urethroplasty (n = 134). Experience navigating the healthcare system with USD (n = 141) and weak urine stream (n = 70) were the most frequent preurethroplasty complaints. Postoperative pain (n = 164) was the most frequent issue. Patients expressed more positivity (n = 126) and satisfaction (n = 120) than negativity (n = 33) with urethroplasty. CONCLUSION: Patients participated in online discussions to share experiences with USD and urethroplasty, receive emotional support, and find answers. Men were more often satisfied than not with their urethroplasty outcomes, with 88% of postoperative feelings coded as positive or satisfied compared to negative. This study provides physicians with insight into the experiences of patients and how to best educate them.

Altruistic donation to improve survey responses: a global randomized trial.

OBJECTIVE: Web-based platforms have revolutionized the ability for researchers to perform global survey research. Methods to incentivize participation have been singularly focused on European and North American participants with varied results. With an ever increasing proportion of biomedical research being performed in non-western countries, assessment of novel methods to improve global survey response is timely and necessary. To that end, we created a three-arm nested randomized control trial (RCT) within a prospective cohort study to assess the impact of incentives on survey responsiveness in a global audience of biomedical researchers. RESULTS: Email invitations were sent to authors and editors involved in online publishing totaling 2426 participants from 111 countries. Overall we observed a 13.0% response rate: 13.3% for the control group, 14.4% for a group entered to win a gift card, and 11.1% for a group whose participation lead to donation to charity (p = 0.17). Year of publication nor country impacted response rate. Within subgroups, editors were significantly less likely to respond to the survey as compared to authors (6.5% vs. 18.9%; p-value < 0.01). With power to detect a 4.8% difference among groups, we could not detect an impact of incentives on global survey response.

The landscape of urological retractions: the prevalence of reported research misconduct.

OBJECTIVES: To evaluate the landscape of retractions of literature and to determine the prevalence of research misconduct in the field of urology. METHODS: Three databases (PUBMED, Embase, Retraction Watch) were queried for all retracted studies on urological topics in both urological and non-urological journals from April 1999 to March 2018. Two reviewers screened the records and determined the final list of articles to be included in the analysis. RESULTS: A total of 138 articles met the inclusion criteria. Over 80% of retractions occurred after 2009. Retractions originated from 76 different journals (13 urological journals) and 28 countries. The most common reasons for retraction were plagiarism (28%), fake peer review (20%), error (20%), and falsification of data (13%). Misconduct accounted for two-thirds of the retractions (n = 93). A large watermark, indicating retraction of the article, was present in 75% of the manuscripts. Articles were cited a total of 4454 times, 38% of citations happened after retraction. The majority of retracted articles related to urological oncology (70%). The highest number of retractions for an individual author was five. Rates of retraction among popular urological journals since 2010 have increased but remain a small proportion of all publications: BJUI, 0.189%; World Journal of Urology, 0.132%; European Urology, 0.058%; Urology, 0.047%; and Journal of Urology, 0.024%. CONCLUSION: Retractions of urological literature, similarly to retractions of other biomedical literature, have been rising over the last decade. The majority of these retractions stem from research misconduct. Despite retractions, flawed articles continued to be cited.

The association of bicycle-related genital numbness and Sexual Health Inventory for Men (SHIM) score: results from a large, multinational, cross-sectional study.

OBJECTIVE: To assess the association of genital numbness and erectile dysfunction in male cyclists. SUBJECTS AND METHODS: Cyclists were recruited through Facebook advertisements and outreach to sporting clubs. This is a secondary analysis of a larger epidemiological population-based study that examined sexual and urinary wellness in athletes. We queried cycling habits and erectile function using Sexual Health Inventory for Men (SHIM). RESULTS: A total of 2 774 male cyclists were included in the analysis. Amongst cyclists, there was a statistically significant increase in the trend of genital numbness presence with more years of cycling (P = 0.002), more frequent weekly cycling (P < 0.001), and longer cycling distance at each ride (P < 0.001). Less frequent use of padded shorts (odds ratio [OR] 0.14, P < 0.001) and lower handlebar (OR 0.49, P < 0.001) were associated with numbness, but body mass index (BMI) (OR 1.1, P = 0.33) and age (OR 1.2, P = 0.15) were not. In a multivariate logistic regression model, after adjusting for age, BMI, and lifetime miles (calculated by average daily cycling mileage × cycling days/week × cycling years.), there were no statistically significant differences in mean SHIM score between cyclists with and cyclists without numbness (20.3 vs 20.2, P = 0.83). However, interestingly, the subset of cyclists who reported numbness in the buttock reported statistically significantly worse SHIM scores (20.3 vs 18.4, P < 0.001). This association was not present in cyclists who reported numbness in the scrotum, penis, or perineum and remained significant after adjusting for overall biking intensity. CONCLUSION: Cyclists report genital numbness in proportion with biking intensity but numbness is not associated with worse sexual function in this cohort.

180° congenital penile torsion with distal hypospadias mistaken for an epispadias: Optimal outcome with tubularized incised plate urethroplasty and dartos flap rotation.

INTRODUCTION: Severe penile torsion of 180° associated with hypospadias is a rare entity. Knowledge of penile anatomy and pathology are necessary as the diagnosis could be missed. CASE PRESENTATION: We report a case of severe 180° penile torsion with distal hypospadias that was mistaken for an epispadias which was corrected with surgery. CONCLUSION: Tubularized incised plate urethroplasty and dartos flap rotation provided satisfactory result for this association.

Minority Recruitment Trends in Phase III Prostate Cancer Clinical Trials (2003 to 2014): Progress and Critical Areas for Improvement.

PURPOSE: American minority groups have been historically underrepresented in phase III prostate cancer clinical trials despite often having higher risk disease. We analyzed enrollment trends of major racial/ethnic groups in the United States in phase III prostate cancer trials between 2003 and 2014 compared to SEER (Surveillance, Epidemiology and End Results) incidence data. MATERIALS AND METHODS: Phase III prostate cancer trials primarily enrolling patients from the United States were identified in the ClinicalTrials.gov database. Enrollment trends were analyzed for major racial/ethnic groups. Prostate cancer incidence data from the SEER registry were used to identify enrollment targets. The enrollment difference was determined by calculating the absolute difference between the percent of a racial/ethnic subgroup in the SEER registry population and the percent of that subgroup in the phase III prostate cancer trial population. RESULTS: Among 39 studies identified African American enrollment in therapeutic trials increased across the study period (p <0.001). The enrollment difference for African Americans was -9.0% (95% CI -7.6- -10.5, p <0.001) in 2003 to 2005 and 1.4% (95% CI 0.2-2.6, p = 0.020) in 2012 to 2014. However, African American men were under enrolled in metastatic disease trials (enrollment difference -5.8%, 95% CI -4.8- -6.8, p <0.001). Latino and Asian American men were consistently under enrolled in all trial types. CONCLUSIONS: Minority groups in the United States were largely under enrolled in phase III prostate cancer trials between 2003 and 2014. While recruitment efforts may have had an impact, as demonstrated by increased enrollment of African American men, there remains a need to expand recruitment efforts to achieve diversity in trials.