Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Breast cancer treatment: A phased approach to implementation.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

Concordance of breast fine needle aspiration cytology interpretation with subsequent surgical pathology: An 18-year review from a single sub-Saharan African institution.

INTRODUCTION: There are many merits to fine needle aspiration cytology (FNAC) in evaluation of palpable breast lesions. We set out to determine the concordance of breast FNAC interpretation with subsequent surgical pathology in the resource-limited healthcare setting of rural Kenya. METHODS: African Inland Church Kijabe Hospital electronic pathology files were retrospectively reviewed from 1/1999-9/2017. All breast FNAC cases and subsequent surgical pathology specimens were identified. FNAC interpretations were categorised according to the International Academy of Cytology Yokohama codes: insufficient; benign; atypical favour benign; suspicious favour malignant; and malignant. Surgical pathology results were categorised as benign or malignant. RESULTS: In total, 695 breast FNACs were identified. A total of 219 (31.5%) had subsequent surgical pathology. Average patient age was 39 years (range 13-88); 95% were female. Nearly all (98%) lesions were palpable. FNAC interpretive categorisation was as follows: 20 (9%) insufficient, 103 (47%) benign, 16 (7%) atypical, 24 (11%) suspicious and 56 (26%) malignant. On histopathology, there were 141 (64%) benign cases and 78 (36%) malignancies (Table 1). The sensitivity of FNAC for detecting malignancy was 85%; specificity was 75%. Positive and negative predictive values were 69% and 88%. Diagnostic concordance between FNAC and histopathology was 79%. For definitively diagnostic FNAC categories, diagnostic concordance was 89%. On histopathology, malignant diagnoses were given in 0 insufficient, 12 (12%) benign, 4 (25%) atypical, 11 (46%) suspicious and 51 (91%) malignant cases. There were five false-positive cytopathology interpretations and 12 false-negatives. CONCLUSIONS: FNAC remains a valuable tool in evaluation of palpable breast lesions in resource-limited healthcare settings.

Ethnicity and breast cancer characteristics in Kenya.

PURPOSE: There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. METHODS: The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. RESULTS: The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p < 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ≥ 5 cm vs. < 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). CONCLUSION: This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa.

Development of a Unifying Target and Consensus Indicators for Global Surgical Systems Strengthening: Proposed by the Global Alliance for Surgery, Obstetric, Trauma, and Anaesthesia Care (The G4 Alliance).

After decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced-based argument for the fundamental role of surgery and anaesthesia within cost-effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.

Rabbit biocontrol and landscape-scale recovery of threatened desert mammals.

Funding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single-species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping-mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241-365%. A threatened marsupial micropredator, the crest-tailed mulgara (Dasycercus cristicauda), underwent a 70-fold increase in extent of occurrence and a 20-fold increase in area of occupancy. Both bottom-up and top-down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit-dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat-category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top-down threat-based management of arid ecosystems. Conservation programs that take big-picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long-term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change.

Cancer referrals at African Inland Church Kijabe Hospital, Kiambu County (2014-2020) and the impact of COVID-19.

In Kenya, cancer is the third leading cause of death. The African Inland Church Kijabe Hospital (AICKH) is a level 4 missionary hospital. The hospital serves the Kenyan population in many areas, including cancer care, and some of these services were affected during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to leverage a recently established hospital-based cancer registry of patients treated at AICKH between 2014 and 2020 to describe the cancer cases and patient referral patterns seen at AICKH during the COVID-19 pandemic in 2020. A cross-sectional retrospective survey was conducted through medical records abstraction in the surgery, breast clinic, palliative care and pathology departments. A total of 3279 cases were included in the study, with females accounting for 58.1% of the cases. The top-three cancers overall were breast (23.0%), oesophagus (20.5%) and prostate (8.6%). There was a minimal increase in the number of cancer cases in 2020 (1.7%) compared with 2019, with an increase of 19.3% in 2019 compared with 2018. In conclusion, AICKH is one of the few hospitals in Kenya where a large number of cancer patients seek healthcare, and referral of cancer cases changed in 2020, which may be due to the COVID-19 pandemic. Future efforts can leverage this registry to determine the impacts of cancer diagnosis and treatment on survival outcomes.

Optimising the Delivery of RHDV to Rabbits for Biocontrol: An Experimental Evaluation of Two Novel Methods of Virus Delivery.

Rabbit haemorrhagic disease virus (RHDV) is established as a landscape-scale biocontrol that assists the management of invasive European rabbits and their impacts in both Australia and New Zealand. In addition to this, it is also available to land managers to augment rabbit control efforts at a local scale. However, current methods of deploying RHDV to rabbits that rely on the consumption of virus-treated baits can be problematic as rabbits are reluctant to consume bait when there is abundant, green, protein-rich feed available. We ran a suite of interrupted time-series experiments to compare the duration of infectivity of two conventional (carrot and oat baits) and two novel (meat bait and soil burrow spray) methods of deploying RHDV to rabbits. All methods effectively killed exposed rabbits. Soil burrow spray and carrot baits resulted in infection and mortality out to 5 days post their deployment in the field, and meat baits caused infection out to 10 days post their deployment. In contrast, oat baits continued to infect and kill exposed rabbits out to 20 days post deployment. Molecular assays demonstrated high viral loads in deployed baits beyond the duration for which they were infectious or lethal to rabbits. Based on our results, we suggest that the drying of meat baits may create a barrier to effective transmission of RHDV by adult flies within 10 days. We therefore hypothesise that fly larvae production and development on infected tissues is critical to prolonged viral transmission from meat baits, and similarly from carcasses of RHDV mortalities, via mechanical fly vectors. Our study demonstrates that meat baits and soil spray could provide additional virus deployment options that remove the need for rabbits to consume baits at times when they are reluctant to do so.

Impact of parallel anesthesia and surgical provider training in sub-Saharan Africa: a model for a resource-poor setting.

BACKGROUND: The lack of appropriate numbers of anesthesia and surgical care providers in many resource-poor countries around the world, especially in rural populations, prevents adequate care of the large numbers of patients who require surgery in these settings. METHODS: This article provides a 10-year review of a rural hospital located in East Africa which developed a training program based on parallel training of anesthesia and surgical care providers. We report the process of building the foundational aspects of a customized medical education program that addresses specific concerns related to the work in a rural African context, which may be very different from medical care provided in the urban settings of low income countries (LIC). We analyzed how the parallel training can provide the clinical tools needed to have a practical impact on the surgical burden in rural Africa. RESULTS: The parallel training program combining training of nurse-anesthetists with the training of multiple levels of surgical care providers, from interns to fellows, led to a fourfold increase in the number of surgical cases. Surgical subspecialty training and the development of an anesthesia care team with anesthesia consultant(s) oversight can serve to maintain a high level of complex and expanding surgical case volume in a rural African hospital setting. CONCLUSIONS: This model can be applied to other similar situations in LIC, where the anesthesia and surgical care can be coupled and then customized for the unique clinical rural setting.

Perspectives from a weary surgical oncologist in Sub-Saharan Africa.

This is an personal reflection on the challenges of managing advanced breast cancer in a resource-poor setting, focussing on financial constraints, unavailability of treatment options, and the personal cost to patient and surgeon.

Is breast cancer from Sub Saharan Africa truly receptor poor? Prevalence of ER/PR/HER2 in breast cancer from Kenya.

OBJECTIVES: Studies on ER/PR/HER2 in breast cancer from Sub Saharan Africa (SSA) are fraught with inconsistencies in the prevalence of hormone receptor status. In Kenya, ER/PR/HER2 for breast cancers is not part of routine assessment and available in only three to four centers across the country. Variability in methodology and interpretation makes comparison between data difficult. Our aim was to accurately determine the prevalence of ER/PR/HER2 using standardized techniques and double reporting. Prognostic tumor parameters were also correlated with clinical features and receptor status. MATERIALS AND METHODS: Consecutive invasive breast cancers (IBC) accrued between September 2011 and December 2012 were analyzed at Aga Khan University Hospital, Nairobi (AKUHN). Tumor blocks were stained for ER/PR/HER2 on an automated platform. Double reporting of ER/PR/HER2 was done using the Allred system and the ASCO/CAP guidelines respectively. RESULTS: A total of 301 cases of IBC were analyzed for pathology and ER/PR/HER2. The age range of patients was 19-94 years with a median of 47.5 years. Invasive ductal carcinoma (NOS) was the most common histologic type (84.2%). ER positivity was seen in 72.8%, PR in 64.8% and HER2 in 17.6% of all cases. Triple negative breast cancers (TNBC) constituted 20.2% of the cases. There was a significant association between receptor status and histologic grade (p < 0.001) and statistically significant trend of increasing pathological stage of tumor (pT) associated with TNBC (p = 0.020). CONCLUSIONS: We present a definitive prospective analysis of ER/PR/HER2 from a single center and demonstrate that prevalence of receptor status from SSA is comparable with that in the West.

Traumatic tracheostomy and spent bullet aspiration after a gunshot injury: a case report.

Penetrating tracheal injuries are rare. Even rarer is the finding of intrabronchial foreign bodies caused by penetrating objects. We report a patient who experienced a gunshot injury to the trachea and mandible. The tracheal wound was debrided and used as a tracheostomy; a spent bullet in the bronchial tree was missed on initial evaluation but later successfully retrieved bronchoscopically. Spent bullet aspiration is a very rare occurrence. A careful examination of radiographs is essential to aid with the diagnosis. Flexible bronchoscopy is the best means of bullet retrieval. Management of any associated injuries is made easier after the airway is secured.

Breast cancer diagnosis in a resource poor environment through a collaborative multidisciplinary approach: the Kenyan experience.

INTRODUCTION: The majority of women with breast cancer in Kenya present with node-positive (stage II) or locally advanced Q7 disease (stage IIIB). Diagnosis is made on fine needle aspirate cytology and treatment is with surgery if resectable. Diagnostic core biopsy is available only at subspecialty hospitals. Processing and reporting of biopsy tissue are not standardised. Hormone receptor and HER2 analyses are rarely done preoperatively. METHODS: As part of a larger study investigating the prevalence of triple negative breast cancer in Kenya, a multidisciplinary workshop of collaborators from 10 healthcare facilities was held. Process gaps were identified, preanalytic variables impacting on ER/PR/HER2 discussed and training in core biopsy provided. Local remedial strategies were deliberated. CONCLUSION: We describe our experience and outcome from the workshop, which can be modelled for other resource poor settings.

Breast cancer management in low resource countries (LRCs): consensus statement from the Breast Health Global Initiative.

The Breast Health Global Initiative (BHGI) brought together international breast cancer experts to discuss breast cancer in low resource countries (LRCs) and identify common concerns reviewed in this consensus statement. There continues to be a lack of public and health care professionals' awareness of the importance of early detection of breast cancer. Mastectomy continues to be the most common treatment for breast cancer; and a lack of surgeons and anesthesia services was identified as a contributing factor in delayed surgical therapy in LRCs. Where available, radiation therapy is still more likely to be used for palliation rather than for curative treatment. Tumor receptor status is often suboptimally performed due to lack of advanced pathology services and variable quality control of tissue handling and processing. Regional pathology services can be a cost-effective approach and can serve as reference, training and research centers. Limited availability of medical oncologists in LRCs often results in non-specialist providing chemotherapeutic services, which requires additional supervision and training. Palliative care is an emerging field in LRCs that requires investment in training and infrastructure development. A commitment and investment in the development of breast cancer care services by LRC governments and health authorities remains a critical need in LRCs.

Mycotic aneurysm of the inferior gluteal artery caused by non-typhi Salmonella in a man infected with HIV: a case report.

INTRODUCTION: Non-typhi Salmonellae infections represent major opportunistic pathogens affecting human immunodeficiency virus-infected individuals residing in sub-Saharan Africa. To the best of our knowledge, we report the first documented case in the medical literature of a Salmonella-induced mycotic aneurysm involving an artery supplying the gluteal region. CASE PRESENTATION: A 37-year-old black, Kenyan man, infected with human immunodeficiency virus with a CD4 count of 132 cells per microliter presented with a pulsatile gluteal mass and debilitating pain progressing over one week. He was receiving prophylaxis with trimethoprim-sulfamethoxazole. Aspiration of the mass yielded gross blood. An ultrasound examination revealed a 37 ml vascular structure with an intra-luminal clot. Upon exploration, a true aneurysm of the inferior gluteal artery was identified and successfully resected. A culture of the aspirate grew a non-typhi Salmonellae species. Following resection, he was treated with oral ciprofloxacin for 10 weeks. He later began anti-retroviral therapy. Forty-two months after the initial diagnosis, he remained alive and well. CONCLUSIONS: Clinicians caring for patients infected with human immunodeficiency virus in Africa and other resource-limited settings should be aware of the invasive nature of Salmonella infections and the potential for aneurysm formation in unlikely anatomical locations. Rapid initiation of appropriate anti-microbial chemotherapy and surgical referral is needed. Use of trimethoprim-sulfamethoxazole prophylaxis does not routinely prevent invasive Salmonella infections.

Trauma in rural Kenya.

BACKGROUND: Trauma in Africa is an increasingly significant problem. The aims of this study were to document the epidemiology and clinical management of trauma in a rural Kenyan hospital and from this to highlight important areas for the medical training of doctors managing trauma in similar situations. METHODS: Prospective audit of 202 consecutive trauma patients admitted to Kijabe Hospital. RESULTS: The mean patient age was 31, 77% were males. The median Injury Severity Score (ISS) was nine. The median distance to hospital was 60 km, with a 9 h delay in presentation. Injury mechanisms included road traffic accidents 52%, fall 22%, assaults 13% and burns 6%. The main injuries were limb fractures, soft tissue injuries, head injury and haemo/pneumothorax. Common interventions included fracture management, wound debridement, chest drain insertion, blood transfusion and skin grafting. The overall mortality rate was 3.5%. CONCLUSION: With appropriate resources and training, good trauma outcomes are possible. The importance of access to hospital care and orthopaedic training are highlighted.

Molecular cloning and characterization of fox testis kinectin.

Kinectin was isolated and characterized from a fox testis cDNA library using a monoclonal antibody (FTA-1) raised against testis surface proteins. The cDNA sequence of 4,479 nucleotides encodes an ORF of 1,330 amino acids (aa) with high homology to mouse, human, and chicken kinectins (GenBank Accession Number AF095786). Southern analysis was used to show that genes homologous to kinectin are present in several mammal species and in at least one marsupial, but not in bacteria. Alternatively spliced forms of fox kinectin were identified, and one of these is uniquely expressed in brain and spleen tissues. Kinectin expression was highest in testis relative to other tissues examined. Sequence analysis and comparisons between species revealed that kinectin encodes multiple alpha-helical coiled coils predicted to form dimers, and is, therefore, likely to exist as a dimer. The results presented in this article suggest that kinectin is required for spermatogenesis, but is not a likely candidate for use in immunocontraceptive vaccines.