Outcome of retained intra-abdominal foreign body managed in a general surgical service in Ibadan: a case series.

Retained intra-abdominal foreign bodies are rare and most occur following abdominal or gynaecological surgery. Sponges are the most retained foreign body. The foreign bodies range from surgical instruments, including abdominal pads and gauze to artery forceps; to a pen cap. Retained objects can also be self-inserted. The authors report a case series on the outcome of retained foreign bodies in the intra-abdominal cavity managed in the general surgery service of the University College Hospital, Ibadan over 12-years.

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Unawareness of breast cancer family history among African women.

Introduction: comprehensive cancer risk assessment services are lacking in most sub-Saharan African countries and the use of accurate family history (FH) information could serve as a cheap strategy for risk evaluation. The aim of this study is to determine the proportion of women unaware of family history of cancer among female relatives and associated socio-demographic characteristics. Methods: using case-control data on breast cancer among 4294 women in Nigeria, Uganda and Cameroon, we investigated the proportion of women unaware of family history of cancer among their female relatives. The association between participants' response to their awareness of female relatives' cancer history and socio-demographic characteristics was analysed according to case-control status, family side and distance of relation. Results: the proportion of women unaware if any relative had cancer was 33%, and was significantly higher among controls (43.2%) compared to 23.9% among cases (p<0.001) (Adjusted Odds Ratio (OR) = 2.51, 95% CI = 2.14 - 2.95). Age, education and marital status remained significantly associated with being unaware of FH among controls on multiple regression. Conclusion: about a third of women interviewed did not know about cancer history in at least one of their female relatives. Efforts aimed at improving cancer awareness in sub-Saharan Africa (SSA) are needed. Our findings could be useful for future studies of cancer risk assessment in SSA.

The promise of data science for health research in Africa.

Data science health research promises tremendous benefits for African populations, but its implementation is fraught with substantial ethical governance risks that could thwart the delivery of these anticipated benefits. We discuss emerging efforts to build ethical governance frameworks for data science health research in Africa and the opportunities to advance these through investments by African governments and institutions, international funding organizations and collaborations for research and capacity development.

Venous Thromboembolism in Hospitalized Patients With Surgical Breast Cancer: Risks and Outcomes.

Background The Caprini risk assessment model has been validated in breast cancer surgery patients. However, its utility in our population has not been described. This study evaluated the benefits and risks of the Caprini risk stratification tool and the incidence of venous thromboembolism (VTE) in the 30-day postoperative period among surgical female patients with breast cancer who were hospitalized during their treatment. Methodology This is a retrospective review of prospectively collected data of all surgical patients with histologically confirmed breast cancer who were hospitalized between January and December 2018. Caprini score, treatment information, and 30-day outcome of prophylaxis were collated and analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results A total of 167 female patients with breast cancer aged 19 to 75 years were hospitalized during the study period. All patients had invasive ductal carcinoma, and the majority (76.6%) were premenopausal. Two fatal VTE events occurred during hospitalization, giving a 30-day incidence of 1.2%. There was no adverse event from chemoprophylaxis. Conclusions VTE is rare in hospitalized surgical patients with breast cancer undergoing routine pharmacologic and mechanical prophylaxis. The Caprini tool can identify extremely low-risk patients who require no prophylaxis.

Effect of a novel pilot support group on distress and quality of life in breast cancer patients in Nigeria.

OBJECTIVE: To assess the effect of a new breast cancer support group (BCSG) on breast cancer patients' self-reported distress and quality of life. METHODS: A single arm pre-post trial providing an eight session healthcare provider led BCSG. Primary outcome variables were distress and quality of life assessed using the National Comprehensive Cancer Network Distress Thermometer (DT) and The Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4), respectively. Topics in each session addressed a wide range of issues some of which were pre-selected by the patients themselves. DATA ANALYSIS: Paired sample t-test was used for data analysis on International Business Machine Statistical Package for the Social Sciences 21. RESULTS: The participants (N = 18) had a mean age of 51. Most had secondary school level education (54%), were traders (59%) and had stage 3 or 4 disease (67%). A larger proportion (78% or n = 14) of the patients lived in rural areas, while 4 (22%) of the patients lived in Ibadan. Out of the 8 sessions, 12 (67%) of the participants attended 1-3 sessions while 6 (33%) attended 4-8 sessions. There were, significant improvements in emotional wellbeing (t = -4.253; p < 0.05) and functional wellbeing (t = -2.191; p < 0.05) on the FACT-B+4. There was a significant reduction in the DT score (t = 2.345; p < 0.05) but the number of items on the problem list were not significantly reduced (t = 1.191; p > 0.05). Majority (75%) of the patients rated the support group activities as satisfactory. CONCLUSION: These data show that the support group can benefit breast cancer patients in terms of reduced distress levels along with satisfaction and improvement in the functional and emotional wellbeing indices of quality of life.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis.

INTRODUCTION: Many diseases of adulthood are associated with a woman's age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations. METHODS: We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria. We undertook a genome-wide association study, and evaluated the performance of previously identified variants. RESULTS: One variant was associated with age at menarche, a deletion at chromosome 2 (chr2:207216165) (p=1.14×10-8). 349 genotyped variants overlapped with these identified in populations of non-African ancestry; these replicated weakly, with 51.9% having concordant directions of effect. However, collectively, a polygenic score constructed of those previous variants was suggestively associated with age at menarche (beta=0.288 years; p=0.041). Further, this association was strong in women enrolled in the USA and Barbados (beta=0.445 years, p=0.008), but not in Nigerian women (beta=0.052 years; p=0.83). DISCUSSION: This study suggests that in women of African ancestry the genetic drivers of age at menarche may differ from those identified in populations of non-African ancestry, and that these differences are more pronounced in women living in Nigeria, although some associated trait loci may be shared across populations. This highlights the need for well-powered ancestry-specific genetic studies to fully characterise the genetic influences of age at menarche.

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.

Feasibility of genetic testing for cancer risk assessment programme in Nigeria.

BACKGROUND: A high frequency of BRCA mutations has been established in Nigerian breast cancer (BC) patients. Recently, patients' and first-degree relatives' interest have been raised on cancer genetic risk assessment through our awareness activities in Nigeria. This led to the emergence of nurse-led cancer genetic counselling (CGC) and testing aimed at providing standard-of-care for individuals at increased risk of hereditary breast and ovarian cancers. METHODS: In June 2018, CGC and testing of patients with BC and ovarian cancer (OC) commenced in collaboration with Color Genomics Inc. for a 30-panel gene testing. Previously trained nurses in CGC at the University College Hospital, Ibadan offered genetic counselling (GC) to willing patients with BC and gynaecological cancer in four out-patient oncology clinics and departments for the pilot study. Consultation consisted of CGC, patient's history, pedigree and sample collection for genetic testing (GT). RESULTS: Forty-seven patients - 40 with BC, five with OC and two with endometrial cancer received GC, and all chose to undergo GT. The average age at testing was 48.2 ± 12.1 years. Eight women reported a known family cancer history and there were more perceived benefits than barriers to GT with the patients experiencing the desire for none of their relative to have cancer. Results revealed no mutations in 27 (57.4%), 16 (4.0%) variants of unknown significance and 4 (8.5%) pathogenic mutations. CONCLUSION: Personalised cancer care utilises GC and testing for cancer risk assessment towards prevention and early detection in high risk women. The study indicates the necessity of expanded cancer genetic services for integration into patient care and cancer prevention.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.

Gossypiboma with perforation of the umbilicus mimicking a complicated urachal cyst: a case report.

BACKGROUND: A retained surgical sponge, also known as a gossypiboma, is a rare cause of serious postoperative complications. Diverse retained surgical materials including instruments such as clamps and sutures have been reported, but surgical sponges are the most common material. We report an unusual case of a gossypiboma mimicking a complicated urachal cyst that led to perforation of the umbilicus. CASE PRESENTATION: A 38-year-old female patient presented in our facility with a palpable periumbilical mass and discharge of pus from the umbilicus for 7 months after an open appendectomy. Since the onset of symptoms, the patient had been treated conservatively in a peripheral hospital where she had been operated on. As no improvement was seen, an ultrasound scan was performed that suggested an intraperitoneal abscess adjacent to the umbilicus. Consequently, the patient was referred to our specialist outpatient department for surgical intervention. Suspecting a complicated urachal cyst, an exploratory laparotomy was performed but revealed a retained surgical sponge as the underlying cause. The gossypiboma was resected, and the postoperative period was unremarkable. CONCLUSION: This case demonstrates that gossypibomas, even though rare, continue to occur. They may clinically and radiologically mimic other pathologies, especially abscesses and tumors. Preventive measures as well as the inclusion of gossypibomas in the differential diagnosis of intraabdominal masses or fistulation detected in patients with a history of surgery are of utmost importance to minimize morbidity, mortality, and potential medicolegal implications.

Impact of axillary node-positivity and surgical resection margins on survival of women treated for breast cancer in Ibadan, Nigeria.

INTRODUCTION: Oncologic surgical extirpation, the mainstay of loco-regional disease control in breast cancer, is aimed at achieving negative margins and lymph node clearance. Even though axillary lymph nodal metastasis is a critical index of prognostication, establishing the impact of lymph node ratio (LNR) and adequate surgical margins on disease-specific survivorship would be key to achieving longer survival. This study examines the prognostic role of pN (lymph nodes positive for malignancy), LNR and resection margin on breast cancer survival in a tertiary hospital in Ibadan, Nigeria. METHODS: We conducted a longitudinal cohort study of 225 patients with breast carcinoma, documented clinico-pathologic parameters and 5-year follow up outcomes - distant metastasis and survival. Chi-square test and logistic regression analysis were used to evaluate the interaction of resection margin and proportion of metastatic lymph nodes with patients' survival. The receiver operating characteristic curve was plotted to determine the proportion of metastatic lymph nodes which predicted survival. The survival analysis was done using Kaplan-Meier method. RESULTS: Sixty (26.7%) patients of the patients had positive resection margins, with the most common immuno-histochemical type being Lumina A. 110 (49%) patients had more than 10 axillary lymph nodes harvested. The mean age was 48.6 ± 11.8 years. Tumour size (p = 0.018), histological type (p = 0.015), grade (p = 0.006), resection margin (p = 0.023), number of harvested nodes (p < 0.01), number of metastatic nodes (p < 0.001) and loco-regional recurrence (p < 0.01) are associated with survival. The overall 5-year survival was 65.3%. CONCLUSION: Unfavourable survival outcomes following breast cancer treatment is multifactorial, including the challenges faced in the multimodal treatment protocol received by our patients.

Breast Cancer Knowledge Assessment of Health Workers in Ibadan, Southwest Nigeria.

PURPOSE: Breast cancer is the most common cancer among women, and in low- to middle-income countries late-stage diagnosis contributes to significant mortality. Previous research at the University College Hospital, a tertiary hospital in Ibadan, Nigeria, on social factors contributing to late diagnosis revealed that many patients received inappropriate initial treatment. METHODS: The level of breast cancer knowledge among health practitioners at various levels of the health system was assessed. We developed a tool tailored to local needs to assess knowledge of symptoms, risk factors, treatments, and cultural beliefs. The recruitment included doctors, nurses, and pharmacists in public hospitals, physicians and pharmacists in private practice, nurses and health care workers from primary health care centers, community birth attendants, and students in a health care field from state schools. RESULTS: A total of 1,061 questionnaires were distributed, and 725 providers responded (68%). Seventy-eight percent were female, and > 90% were Yoruba, the dominant local ethnic group. The majority were Christian, and 18% were Muslim. Median knowledge score was 31 out of 56, and the differences in scores between health care worker types were statistically significant (P < .001). Nearly 60% of the participants believed breast cancer is always deadly. More than 40% of participants believed that keeping money in the bra causes breast cancer, and approximately 10% believed that breast cancer is caused by a spiritual attack. CONCLUSION: Our questionnaire revealed that, even at the tertiary care level, significant gaps in knowledge exist, and knowledge of breast cancer is unacceptably low at the level of community providers. In addition to efforts aimed at strengthening health systems, greater knowledge among community health care workers has the potential to reduce delays in diagnosis for Nigerian patients with breast cancer.

Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h2 = 0.575, p = 0.010) and the combined APOBEC signatures (h2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10-6 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.

Outcome of Cerebral Metastasectomy in Select Cases of Brain Metastases from Breast Cancer in Ibadan, Nigeria.

BACKGROUND: Brain metastasis (BM) from breast cancer is increasingly encountered clinically because of the continuing success in the oncological control of the primary disease. Data-driven reports on the surgical treatment of BM from breast cancer are sparse in sub-Saharan Africa. METHODS: This is a prospective cohort study of the outcome of surgical excision of BM from breast cancer in an academic surgical practice in Ibadan, Nigeria. RESULTS: A total of 12 consecutive cerebral metastasectomies, all in females with primary breast cancer, were recorded over the study period. The median age (range) at breast cancer diagnosis was 41 (27-72) years, and the time interval from primary disease to BM was 19 (12-29) months. The BM was the first site of systemic disease progression in all, and was heralded by headache, seizures, and hemiparesis in more than two-thirds of the patients. The brain lesions were multiple in a quarter: >4 cm large in 42% and were located supratentorial in >80%. They all achieved good recovery and in-hospital outcome after surgical lesionectomy-infra- and supratentorial craniotomies-but only two-thirds could access postsurgical adjuvant whole brain radiation therapy. Median survival after cerebral metastasectomy was 18 (11-55) months, and more than a quarter were alive for ≥3years. These survival statistics were significantly better than those of a contemporary cohort of our patients with breast cancer who also had BMs that were not surgically treated for various clinical and logistic limitations. CONCLUSIONS: Surgical resection is feasible for BM from breast cancer even in low-resource clinical practice. It has a salutary effect on the patients' quality of life.

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

Knowledge of Genetic Counseling Among Patients With Breast Cancer and Their Relatives at a Nigerian Teaching Hospital.

Breast cancer prevalence continues to increase globally, and a significant proportion of the disease has been linked to genetic susceptibility. As we enter the era of precision medicine, genetics knowledge and skills are increasingly essential for achieving optimal cancer prevention and care. However, in Nigeria, patients with breast cancer and their relatives are less knowledgeable about genetic susceptibility to chronic diseases. This pilot study collected qualitative data during in-depth interviews with 21 participants. Of these, 19 participants were patients with breast cancer and two were relatives of patients with breast cancer. Participants were asked questions regarding their knowledge of breast cancer, views on heredity and breast cancer, and views on genetic counseling. Participants' family histories were used as a basis with which to assess their hereditary risk of breast cancer. Participant responses were audio recorded and transcribed manually. The study evaluated patients' and relatives' knowledge of genetic counseling and the use of family history for the assessment of familial risk of breast cancer. This will serve as a guide to the processes of establishing a cancer risk assessment clinic.