Competency-Based Workforce Development and Education in Global Oncology.

The healthcare workforce plays a pivotal role in cancer care delivery, leadership, policy, education, and research in complex cancer systems. To ensure quality and relevance, health professionals must have the necessary competencies to deliver patient-centered and efficient care, coupled with the ability to work in teams and manage health resources wisely. This paper aims to review the concept of competency-based medical education (CBME) in the context of oncology to provide insights and guidance for those interested in adopting or adapting competency-based education in training programs. The results of a scoping review of CBME in oncology are presented here to describe the current status of CBME in oncology. The literature describing the implementation and evaluation of CBME in oncology training programs for medical professionals internationally is summarized and key themes identified to provide practical guidance for educators. Further, the paper identifies critical competencies for oncology education and training globally and presents recommendations and opportunities for collaboration in competency-based education and training in oncology. The authors argue for increased global collaboration and networking in the realm of CBME to facilitate the establishment of a competent global cancer care workforce.

A Bone Scan Is Valuable for Primary Staging of Newly Diagnosed Prostate Cancer in a Low-Resource Setting (Nigeria).

Objective: There is a paucity of information on bone scanning for prostate cancer from low-resource countries. This study evaluated the role of bone scan in the primary staging of newly diagnosed prostate cancer in one such setting. Methods: A retrospective analysis of 126 men with newly diagnosed prostate cancer undergoing an initial staging bone scan between January 2017 and December 2020 was carried out at a regional nuclear medicine center in Nigeria. Bone scan results were analyzed according to age, serum level of baseline prostate-specific antigen (PSA), and Gleason score. Equivocal scans and patients with no Gleason score or baseline PSA were excluded from the analysis. p < 0.05 was said to be significant statistically. Results: Of 111 patients (aged 38-84 years, median 66 years), who met the inclusion criteria, 26 (23%) men had evidence of bony metastases as shown by a positive bone scan. Higher PSA levels and Gleason scores were associated with an increased risk of a positive bone scan, p < 0.001. No patient with a PSA level < 20 ng/mL and a Gleason score of < 7 had a positive bone scan. Conclusion: The role of bone scanning in staging newly diagnosed prostate cancer patients in Nigeria is consistent with global reports. Our study confirms that a bone scan finding is well associated with the risk classification using PSA and Gleason score in our population.

MicroRNA-1205 Regulation of FRYL in Prostate Cancer.

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors in vivo. To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced in vitro and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.

Population Differentiation at the PVT1 Gene Locus: Implications for Prostate Cancer.

Genetic variation in susceptibility to complex diseases, such as cancer, is well-established. Enrichment of disease associated alleles in specific populations could have implications for disease incidence and prevalence. Prostate cancer (PCa) is a disease with well-established higher incidence, prevalence, and worse outcomes among men of African ancestry in comparison to other populations. PCa is a multi-factorial, complex disease, but the exact mechanisms for its development and progression are unclear. The gene desert located on chromosome 8q24 is associated with aggressiveness of PCa. Interestingly, the non-protein coding gene locus Plasmacytoma Variant Translocation (PVT1) is present at chromosome 8q24 and is overexpressed in PCa. PVT1 gives rise to multiple transcripts with potentially different molecular and cellular functions. In an analysis of the PVT1 locus using data from the 1000 Genomes Project, we found the chromosomal region spanning PVT1 exons 4A and 4B to be highly differentiated between African and non-African populations. We further investigated levels of gene expression of PVT1 exons 4A and 4B and observed significant overexpression of these exons in PCa tissues relative to benign prostatic hyperplasia and to normal prostate tissues obtained from men of African ancestry. These results indicate that PVT1 exons 4A and 4B may have clinical implications in PCa a conclusion supported by the observation that transient and stable overexpression of PVT1 exons 4A and 4B significantly induce greater prostate epithelial cell migration and proliferation. We anticipate that further exploration of the role of PVT1 exons 4A and 4B may lead to the development of diagnostic, therapeutic, and other clinical applications in PCa.

Long Noncoding RNA from PVT1 Exon 9 Is Overexpressed in Prostate Cancer and Induces Malignant Transformation and Castration Resistance in Prostate Epithelial Cells.

Prostate cancer (PCa) is the most common non-cutaneous cancer and second leading cause of cancer-related death for men in the United States. The nonprotein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in different cancers. PVT1 gives rise to several alternatively spliced transcripts and microRNAs. There are at least twelve exons of PVT1, which make separate transcripts, and likely have different functions. Here, we demonstrate that PVT1 exon 9 is significantly overexpressed in PCa tissues in comparison to normal prostate tissues. Both transient and stable overexpression of PVT1 exon 9 significantly induced greater prostate epithelial cell migration, as well as increased proliferation and corresponding proliferating cell nuclear antigen (PCNA) expression. Notably, implantation into mice of a non-tumorigenic prostate epithelial cell line stably overexpressing PVT1 exon 9 resulted in the formation of malignant tumors. Furthermore, PVT1 exon 9 overexpression significantly induced castration resistance. Consequently, PVT1 exon 9 expression is important for PCa initiation and progression, and holds promise as a therapeutic target in PCa.

PVT1 Signaling Is a Mediator of Cancer Progression.

There is increasing evidence that PVT1 has oncogenic properties and regulates proliferation and growth of many cancers. Themolecular mechanisms of action of PVT1 are mediated, in part, by microRNAs (miRNAs). However, some well-established transcription factors involved in cancer cell proliferation share a common thread of microRNA associations with PVT1. Furthermore, these microRNAs are also involved in mechanisms that lead to the development of drug resistance in cancer cells. While several microRNAs have been implicated directly in PVT1-mediated tumorigenesis, significant steps need to be taken to elucidate these important relationships. We synthesize the current knowledge of the miRNAs and associated genes by which PVT1 contributes to tumorigenesis. Overall, the trend suggests a negative correlation of microRNA expression with PVT1. It is clear that future studies involving PVT1 should be carried out in conjunction with microRNA analysis and should include large scale lncRNA-miRNA-mRNA network analysis. Likewise, the relationship between established transcription factors such as p53 and MYC, and processes like epithelial-mesenchymal transition may offer valuable insight into the yet unknown mechanisms of PVTI-mediated cancer progression via microRNA-dependent signaling networks.

Bilateral double ureters with bladder neck diverticulum in a nigerian woman masquerading as an obstetric fistula.

A 43-year-old woman presented with 20-year history of leakage of urine per vaginam. She had one failed repair attempt. Pelvic examination with dye test showed leakage of clear urine suggestive of ureterovaginal fistula. The preoperative intravenous urogram revealed duplex ureter and cystoscopy showed normally cited ureteric orifices with two other ectopic ureteric openings and bladder diverticula. The definitive surgery performed was ureteric reimplantation (ureteroneocystostomy) of the two distal ureteric to 2 cm superiolateral to the two normal orifices and diverticuloplasty. There was resolution of urinary incontinence after surgery. Three months after surgery, she had urodynamic testing done (cystometry), which showed 220 mLs with no signs of instability or leakage during filling phase but leaked on coughing at maximal bladder capacity. This is to showcase some diagnostic dilemma that could arise with obstetric fistula, which is generally diagnosed by clinical assessment.

Management of advanced prostate cancer in Africa.

BACKGROUND: Carcinoma of the prostate (CaP) is the most common male malignancy in developed and developing countries and has been termed the "malignant epidemic of blacks." Despite this, clinicians managing men with advanced CaP in Africa have to contend with significant limitations in the healthcare systems. This article reviews the current and future options for the management of these patients on the African continent. METHODS: We searched PubMed and Google for articles on CaP with an emphasis on those focusing on subpopulation differences. Information was also obtained from ongoing studies and interviews with urologists and other specialists and executives in hospitals in our locality. RESULTS: In Africa, most patients with CaP present with advanced disease, and surgical castration is the most common treatment option, as most modern treatment strategies for the disease are unavailable or unaffordable. Unfortunately, a significant proportion of these men progress to hormone-resistant disease shortly after first-line hormonal treatment, and a majority die within 2 years. Problems that are peculiar to the African continent include poor health facilities, scarcity of expert care, high cost of treatment, lack of data, low level of awareness of the disease, absence of early detection and treatment programs, cultural limitations, and the prominence of alternative medical practice. CONCLUSION: Most Africans with CaP present with advanced disease, and treatment is mostly limited to bilateral orchiectomy, but the results are poor. The care of these patients can be improved by increased funding of healthcare institutions and projects directed at prevention, early detection, and treatment.

Androgen receptor protein expression in prostatic tissues in Black and Caucasian men.

BACKGROUND: CaP has a higher incidence and mortality in Black men. We hypothesized that subpopulation differences in AR expression may contribute to this phenomenon. METHOD: AR immunostaining was compared in epithelium and PES of normal, BPH, and CaP tissues from Black African men and UK Caucasian men. RESULTS: AR expression was similar in normal prostatic epithelium of both groups, but was higher in BPH and CaP epithelium of Black than Caucasian men (P