Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

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.

A case of pyelo-ureteral junction bilharzioma.

Bilharziomas are inflammatory tumour-like masses which often pose the problem of differential diagnosis with neoplastic processes. Its location at the pyelo-ureteral junction is very uncommon. The pre-operative diagnosis of bilharzia of the pyelo-ureteral junction is difficult. Indeed, the diagnosis is most often made on anatomo-pathological examination of the surgical specimen, which rarely allows for conservative treatment. We report one case of pyeloureteral junction bilharzioma in children living in bilharzia endemic areas and discuss the diagnostic and therapeutic issues of these cases.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Effective Project Management of a Pan-African Cancer Research Network: Men of African Descent and Carcinoma of the Prostate (MADCaP).

PURPOSE: Health research in low- and middle-income countries can generate novel scientific knowledge and improve clinical care, fostering population health improvements to prevent premature death. Project management is a critical part of the success of this research, applying knowledge, skills, tools, and techniques to accomplish required goals. Here, we describe the development and implementation of tools to support a multifaceted study of prostate cancer in Africa, focusing on building strategic and operational capacity. METHODS: Applying a learning organizational framework, we developed and implemented a project management toolkit (PMT) that includes a management process flowchart, a cyclical center-specific schedule of activities, periodic reporting and communication, and center-specific monitoring and evaluation metrics. RESULTS: The PMT was successfully deployed during year one of the project with effective component implementation occurring through periodic cycles of dissemination and feedback to local center project managers. A specific evaluation was conducted 1 year after study initiation to obtain enrollment data, evaluate individual quality control management plans, and undertake risk log assessments and follow-up. Pilot data obtained identified areas in which centers required mentoring, strengthening, and capacity development. Strategies were implemented to improve project goals and operational capacity through local problem solving, conducting quality control checks and following compliancy with study aims. Moving forward, centers will perform quarterly evaluations and initiate strengthening measures as required. CONCLUSION: The PMT has fostered the development of both strategic and operational capacity across project centers. Investment in project management resources is essential to ensuring high-quality, impactful health research in low- and middle-income countries.

Development, Evaluation, and Implementation of a Pan-African Cancer Research Network: Men of African Descent and Carcinoma of the Prostate.

PURPOSE: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. METHODS: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. RESULTS: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. CONCLUSION: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Global cancer surgery: delivering safe, affordable, and timely cancer surgery.

Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US $6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.

Surgical outcomes and cultural perceptions in international hypospadias care.

PURPOSE: This study was designed to assess perceptions of untreated hypospadias and quality of life in culturally disparate low or middle income countries, to highlight the demographic and care differences of patient groups treated for hypospadias in the surgical workshop context, and to evaluate the long-term outcomes achieved by these workshop groups. MATERIALS AND METHODS: Family member perceptions of hypospadias, perioperative process measures and urethrocutaneous fistula rates were compared between 60 patients from Vietnam and Senegal treated for hypospadias through training workshops by local surgeons and pediatric urologists from the U.S. between 2009 and 2012, of whom approximately 42% had previously undergone repair attempts. RESULTS: More than 90% of respondents surveyed believed that untreated hypospadias would affect the future of their child at least to some degree. Patient cohorts between the 2 sites differed from each other and published high income country cohorts regarding age, weight for age and frequency of reoperation. Telephone based outcomes assessment achieved an 80% response rate. Urethrocutaneous fistula was reported in 39% and 47% of patients in Vietnam and Senegal, respectively. CONCLUSIONS: Family members perceived that the social consequences of untreated hypospadias would be severe. Relative to patient cohorts reported in practices of high income countries, our patients were older, presented with more severe defects, required more reoperations and were often undernourished. Urethrocutaneous fistula rates were higher in cohorts from low or middle income countries relative to published rates for cohorts from high income countries. Our study suggests that outcomes measurement is a feasible and essential component of ethical international health care delivery and improvement.

[Testicular cancer is a rare condition in black people. We report 5 cases of testicular cancer in men with undescended testis]. / Cancer sur testicule non descendu intra-abdominal. A propos de 5 cas.

PATIENTS AND METHODS: We underwent a retrospective study of five cases of testicular cancer in undescended testis. The parameters of study were: age at diagnosis, circumstances of diagnosis, values of tumour markers, and pathological aspects of tumours after removal. The data were studied using the medical records of patients. RESULTS: Mean age was 30, 6 years (27; 34). Only 1 patient had a child at the time of diagnosis. All patients came to our clinic for a general state impairment associated to an abdominal palpable mass. The increase of the value of tumour markers was not constant. A capsular effraction was found in 3 cases with a rupture into the peritoneum. The pathology exam found 3 embryonic carcinoma and 2 seminomas, a lymph node involvement was found in 3 cases. CONCLUSION: The scarcity of these tumours should not make us ignore them. The early diagnosis of the tumour can be facilitated by testicular descent, because even if the descent of the testis does not prevent the tumour it can ease the follow-up.

[Leiomyosarcoma of the spermatic cord]. / Le léiomyosarcome du cordon spermatique.

Leiomyosarcomas of the spermatic cord are rare tumours. The authors report the case of a 65-year-old man presenting with painful mass of the left side of the scrotum with scrotal ulceration. Left transinguinal orchidectomy and left hemiscrotectomy were performed and histological examination of the operative specimen revealed leiomyosarcoma of the spermatic cord. No metastases were observed on thoracoabdominopelvic CT. One month after discharge from hospital, the patient presented with delayed healing and complementary scrotal resection and adjuvant radiotherapy were performed. Local and regional extension is frequently observed in leiomyosarcoma of the spermatic cord, justifying radical transinguinal orchidectomy with high ligation of the cord. Cases at greatest risk of recurrence (large tumour, early local recurrence, positive surgical margins) should be identified by multidisciplinary committees and may be eligible for adjuvant radiotherapy.