The African Research Group for Oncology: A decade fostering colorectal cancer research in Nigeria.

The African Research Group for Oncology (ARGO) was formed in 2013 to undertake methodologically rigorous cancer research in Nigeria, and to strengthen cancer research capacity in the country through training and mentorship of physicians, scientists, and other healthcare workers. Here, we describe how ARGO's work in colorectal cancer (CRC) has evolved over the past decade. This includes the consortium's scientific contributions to the understanding of CRC in Nigeria and globally and its research capacity-building program.

Ensuring Global Access to Cancer Medicines: A Generational Call to Action.

SUMMARY: Essential cancer treatments are not accessible, affordable, or available to patients who need them in many parts of the world. A new Access to Oncology Medicines (ATOM) Coalition, using public-private partnerships, aims to bring essential cancer medicines and diagnostics to patients in low- and lower middle-income countries.

Colorectal cancer screening with fecal immunochemical testing: a community-based, cross-sectional study in average-risk individuals in Nigeria.

BACKGROUND: The estimated incidence of colorectal cancer is rising in Nigeria, where most patients present with advanced disease. Earlier detection of colorectal cancer is a goal of the Nigerian National Cancer Control Plan, but the utility of fecal-based screening is unclear. This study aimed to assess the fecal immunochemical test as a colorectal cancer screening modality in average-risk individualS in Nigeria. METHODS: A population-based, cross-sectional study of qualitative fecal immunochemical test-based colorectal cancer screening was done in asymptomatic, average-risk participants aged 45-75 years in three states in Nigeria (Osun, Kwara, and Lagos). Participants were invited to enrol using age-stratified and sex-stratified convenience sampling following community outreach. Exclusion criteria included a personal history of colorectal cancer or rectal bleeding in the previous 6 months, a first-degree relative with a known diagnosis of colorectal cancer, or a comorbidity that would preclude conscious sedation or general anesthesia. Participants with positive fecal immunochemical test results underwent colonoscopy, and the positive predictive value of fecal immunochemical testing for colorectal cancer and advanced adenomas (≥10 mm, tubulovillous or villous or high-grade dysplasia) was calculated. Data on demographics and acceptability of fecal immunochemical testing and colonoscopy were collected. FINDINGS: Between January and April 2021, 2330 participants were enrolled in the study and received a fecal immunochemical test, which was returned by 2109 participants. 1677 participants tested negative and 432 tested positive. Of these 432 participants, 285 underwent a colonoscopy (235 showed no polyps or cancer, 47 had polyps identified, and three had colorectal cancer identified). Of the 47 participants who had polyps identified, 20 had advanced adenomas diagnosed. The median age was 57 years (IQR 50-63), 958 (41%) were male and 1372 (59%) were female, and 68% had at least a secondary-level education. Participants were evenly spread across wealth quintiles. The positivity rate of the fecal immunochemical test was 21% overall (432 of 2109; 95% CI 20-21%), 11% (51 of 455; 95% CI 10-12) in Lagos, 20% (215 of 1052; 95% CI 20-21) in Osun, and 28% (166 of 597; 95% CI 27-29) in Kwara. Among the patients with a positive fecal immunochemical test who completed colonoscopy, the positive predictive value for invasive colorectal cancer was 1·1% (95% CI 0·3-3·3), and 7·0% (4·5-10·8) for advanced adenoma. The acceptability of fecal immunochemical screening among participants was very high. INTERPRETATION: Colorectal cancer screening with qualitative fecal immunochemical tests in Nigeria is feasible and acceptable to average-risk asymptomatic participants. However, the low positive predictive value for advanced neoplasia and high endoscopy burden investigating false positives suggests it might not be an appropriate screening tool in this setting. FUNDING: Thompson Family Foundation, Prevent Cancer Foundation, National Institutes of Health/National Cancer Institute Program Cancer Center.

Priorities for cancer research in low- and middle-income countries: a global perspective.

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public.

Growing academic global surgery: opportunities for Canadian trainees.

SummaryGlobal surgery has seen exponential growth over the past few years, and Canadian trainees' interest in the field has followed. Global surgery is defined by a commitment to health equity and community partnership. Engagement with its core principles is relevant for all Canadian surgical trainees and offers a perspective into inequities in surgical access and outcomes for patients and communities, both locally and globally. Several opportunities in academic global surgery for trainees have emerged in Canada, but appear to be underutilized. This article highlights existing Canadian global surgery initiatives, including formal postgraduate curricula, research and policy collaborations, trainee networks, advocacy projects, dedicated fellowships, and conferences. We identify areas in which institutions and departments of surgery can better support trainees in exploring each of these categories during training. Canadian trainees' exposure to global surgery can nurture their roles as future health advocates, communicators, and leaders locally and beyond.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

High-burden Cancers in Middle-income Countries: A Review of Prevention and Early Detection Strategies Targeting At-risk Populations.

Cancer incidence is rising in low- and especially middle-income countries (MIC), driven primarily by four high-burden cancers (breast, cervix, lung, colorectal). By 2030, more than two-thirds of all cancer deaths will occur in MICs. Prevention and early detection are required alongside efforts to improve access to cancer treatment. Successful strategies for decreasing cancer mortality in high-income countries are not always effective, feasible or affordable in other countries. In this review, we evaluate strategies for prevention and early detection of breast, cervix, lung, and colorectal cancers, focusing on modifiable risk factors and high-risk subpopulations. Tobacco taxation, human papilloma virus vaccination, cervical cancer screen-and-treat strategies, and efforts to reduce patient and health system-related delays in the early detection of breast and colorectal cancer represent the highest yield strategies for advancing cancer control in many MICs. An initial focus on high-risk populations is appropriate, with increasing population coverage as resources allow. These strategies can deliver significant cancer mortality gains, and serve as a foundation from which countries can develop comprehensive cancer control programs. Investment in national cancer surveillance infrastructure is needed; the absence of national cancer data to identify at-risk groups remains a barrier to the development of context-specific cancer control strategies.

Abdominal neoplastic manifestations of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary tumor syndrome, with a wide clinicopathologic spectrum. It is defined by characteristic central nervous system, cutaneous and osseous manifestations, and by mutations in the NF1 gene, which is involved in proliferation via p21, RAS, and MAP kinase pathways. Up to 25% of NF1 patients develop intra-abdominal neoplastic manifestations including neurogenic (commonly plexiform neurofibromas and malignant peripheral nerve sheath tumors), interstitial cells of Cajal (hyperplasia, gastrointestinal stromal tumors), neuroendocrine, and embryonal tumors (rhabdomyosarcoma). Nonspecific symptoms, multifocal disease, or coexistence of 2 or more tumor types make patients challenging to diagnose and manage. Screening for intra-abdominal tumors in NF1 patients remains controversial, and currently no guidelines are established. Management decisions are complex and often informed by single-center experiences or case studies in the literature, though the field is rapidly evolving. Thus, NF1 patients should be followed in specialist centers familiar with their wide spectrum of pathology and with multidisciplinary care including specialized pathology and radiology. This review will (1) provide a contemporaneous synthesis of the literature and our multi-institutional clinical experiences with intra-abdominal neoplasms in NF1 patients, (2) present a classification framework for this heterogeneous group of disorders, and (3) outline approaches to screening, surveillance, diagnosis, and management.

External injuries, trauma and avoidable deaths in Agincourt, South Africa: a retrospective observational and qualitative study.

OBJECTIVE: Injury burden is highest in low-income and middle-income countries. To reduce avoidable deaths, it is necessary to identify health system deficiencies preventing timely, quality care. We developed criteria to use verbal autopsy (VA) data to identify avoidable deaths and associated health system deficiencies. SETTING: Agincourt, a rural Bushbuckridge municipality, Mpumalanga Province, South Africa. PARTICIPANTS: Agincourt Health and Socio-Demographic Surveillance System and healthcare providers (HCPs) from local hospitals. METHODS: A literature review to explore definitions of avoidable deaths after trauma and barriers to access to care using the 'three delays framework' (seeking, reaching and receiving care) was performed. Based on these definitions, this study developed criteria, applicable for use with VA data, for identifying avoidable death and which of the three delays contributed to avoidable deaths. These criteria were then applied retrospectively to the VA-defined category external injury deaths (EIDs-a subset of which are trauma deaths) from 2012 to 2015. The findings were validated by external expert review. Key informant interviews (KIIs) with HCPs were performed to further explore delays to care. RESULTS: Using VA data, avoidable death was defined with a focus on survivability, using level of consciousness at the scene and ability to seek care as indicators. Of 260 EIDs (189 trauma deaths), there were 104 (40%) avoidable EIDs and 78 (30%) avoidable trauma deaths (41% of trauma deaths). Delay in receiving care was the largest contributor to avoidable EIDs (61%) and trauma deaths (59%), followed by delay in seeking care (24% and 23%) and in reaching care (15% and 18%). KIIs revealed context-specific factors contributing to the third delay, including difficult referral systems. CONCLUSIONS: A substantial proportion of EIDs and trauma deaths were avoidable, mainly occurring due to facility-based delays in care. Interventions, including strengthening referral networks, may substantially reduce trauma deaths.

Geospatial, racial, and educational variation in firearm mortality in the USA, Mexico, Brazil, and Colombia, 1990-2015: a comparative analysis of vital statistics data.

BACKGROUND: Firearm mortality is a leading, and largely avoidable, cause of death in the USA, Mexico, Brazil, and Colombia. We aimed to assess the changes over time and demographic determinants of firearm deaths in these four countries between 1990 and 2015. METHODS: In this comparative analysis of firearm mortality, we examined national vital statistics data from 1990-2015 from four publicly available data repositories in the USA, Mexico, Brazil, and Colombia. We extracted medically-certified deaths and underlying population denominators to calculate the age-specific and sex-specific firearm deaths and the risk of firearm mortality at the national and subnational level, by education for all four countries, and by race or ethnicity for the USA and Brazil. Analyses were stratified by intent (homicide, suicide, unintentional, or undetermined). We quantified avoidable mortality for each country using the lowest number of subnational age-specific and period-specific death rates. FINDINGS: Between 1990 and 2015, 106·3 million medically-certified deaths were recorded, including 2 472 000 firearm deaths, of which 851 000 occurred in the USA, 272 000 in Mexico, 855 000 in Brazil, and 494 000 in Colombia. Homicides accounted for most of the firearm deaths in Mexico (225 000 [82·7%]), Colombia (463 000 [93·8%]), and Brazil (766 000 [89·5%]). Suicide accounted for more than half of all firearm deaths in the USA (479 000 [56·3%]). In each country, firearm mortality was highest among men aged 15-34 years, accounting for up to half of the total risk of death in that age group. During the study period, firearm mortality risks increased in Mexico and Brazil but decreased in the USA and Colombia, with marked national and subnational geographical variation. Young men with low educational attainment were at increased risk of firearm homicide in all four countries, and in the USA and Brazil, black and brown men, respectively, were at the highest risk. The risk of firearm homicide was 14 times higher in black men in the USA aged 25-34 years with low educational attainment than comparably-educated white men (1·52% [99% CI 1·50-1·54] vs 0·11% [0·10-0·12]), and up to four times higher than in comparably-educated men in Brazil, Colombia, and Mexico. In the USA, the risk of firearm homicide was more than 30 times higher in black men with post-secondary education than comparably educated white men. If countries could achieve the same firearm mortality rates nationally as in their lowest-burden states, 1 777 800 firearm deaths at all ages and in both sexes could be avoided, including 1 028 000 deaths in men aged 15-34 years. INTERPRETATION: Firearm mortality in the USA, Mexico, Brazil, and Colombia is highest among young adult men, and is strongly associated with race and ethnicity, and low education levels. Reductions in firearm deaths would improve life expectancy, particularly for black men in the USA, and would reduce racial and educational disparities in mortality. FUNDING: Canadian Institutes of Health Research and the University of Toronto Connaught Global Challenge.

Perioperative therapies - Enhancing the impact of cancer surgery with repurposed drugs.

Surgical resection remains the major modality for modern curative treatment for solid tumours. However, post-surgical recurrence, even following clear-margin resection and adjuvant treatment, remains common in many types of cancer. Reducing recurrence rates, therefore, offers the potential to increase cure rates and increase overall survival. Perioperative therapies, simple interventions during the perioperative period, are designed to address some of the factors which influence post-surgical recurrence. A range of perioperative therapies are introduced and the rationale for further clinical investigation outlined.

Renal failure deaths and their risk factors in India 2001-13: nationally representative estimates from the Million Death Study.

BACKGROUND: Renal failure represents a growing but mostly undocumented cause of premature mortality in low-income and middle-income countries. We investigated changes in adult renal failure mortality and its key risk factors in India using the nationally representative Million Death Study. METHODS: In this cross-sectional analysis of population-based data, two trained physicians independently assigned underlying causes to 150 018 deaths at ages 15-69 years from a nationally-representative mortality survey in India for 2001-03 and 2010-13, using the International Classification of Diseases, 10th version (ICD-10). We applied the age-specific proportion of renal failure deaths for the 2010-13 period to the 2015 UN estimates of total deaths in India and calculated age-standardised death rates for renal failure by rural or urban residence, state, and age group. We used proportional mortality of renal deaths (cases) to injuries (controls) to calculate the odds of renal death in the presence of different comorbidities and stratified risks by decade of birth. FINDINGS: In 2001-03, 2·1% of total deaths among 15-69 year olds were from renal failure (1266 [2·2%] of 58 871; unweighted). By 2010-13, the proportion of deaths from renal failure had risen to 2·9% (2943 [3·2%] of 91 147; unweighted) of total deaths and corresponding to 136 000 renal failure deaths (range 108 000-150 000) of 4 688 000 total deaths nationally in 2015. Age-standardised renal death rates were highest in the southern and eastern states, particularly among adults aged 45-69 years in 2010-13. Diabetes, hypertension, and cardiovascular disease were all significantly associated with increased renal failure deaths, with diabetes the strongest predictor-odds ratio (OR) vs control 9·2 (95% CI 6·7-12·7) in 2001-03, rising to 15·1 (12·6-18·1) in 2010-13. In the 2010-13 study population, the diabetes to non-diabetes OR was twice as large in adults born in the 1970s (25·5, 95% CI 17·6-37·1) as in those individuals born during or before the 1950s (11·7, 9·1-14·9). INTERPRETATION: Renal failure is a growing cause of premature death in India. Poorly treated diabetes is the most probable reason for this increase. Strategies aimed at diabetes prevention, and early detection and treatment are urgently needed in India, as well as greater access to renal replacement therapy. FUNDING: US National Institutes of Health, International Development Research Centre, Centre for Global Health Research, University of Toronto.

Financial contributions to global surgery: an analysis of 160 international charitable organizations.

BACKGROUND: The non-profit and volunteer sector has made notable contributions to delivering surgical services in low-and middle-income countries (LMICs). As an estimated 55 % of surgical care delivered in some LMICs is via charitable organizations; the financial contributions of this sector provides valuable insight into understanding financing priorities in global surgery. METHODS: Databases of registered charitable organizations in five high-income nations (United States, United Kingdom, Canada, Australia, and New Zealand) were searched to identify organizations committed exclusively to surgery in LMICs and their financial data. For each organization, we categorized the surgical specialty and calculated revenues and expenditures. All foreign currency was converted to U.S. dollars based on historical yearly average conversion rates. All dollars were adjusted for inflation by converting to 2014 U.S. dollars. RESULTS: One hundred sixty organizations representing 15 specialties were identified. Adjusting for inflation, in 2014 U.S. dollars (US$), total aggregated revenue over the years 2008-2013 was $3·4 billion and total aggregated expenses were $3·1 billion. Twenty-eight ophthalmology organizations accounted for 45 % of revenue and 49 % of expenses. Fifteen cleft lip/palate organizations totaled 26 % of both revenue and expenses. The remaining 117 organizations, representing a variety of specialties, accounted for 29 % of revenue and 25 % of expenses. In comparison, from 2008 to 2013, charitable organizations provided nearly $27 billion for global health, meaning an estimated 11.5 % went towards surgery. CONCLUSION: Charitable organizations that exclusively provide surgery in LMICs primarily focus on elective surgeries, which cover many subspecialties, and often fill deep gaps in care. The largest funding flows are directed at ophthalmology, followed by cleft lip and palate surgery. Despite the number of contributing organizations, there is a clear need for improvement and increased transparency in tracking of funds to global surgery via charitable organizations.

Prioritizing Surgical Care on National Health Agendas: A Qualitative Case Study of Papua New Guinea, Uganda, and Sierra Leone.

BACKGROUND: Little is known about the social and political factors that influence priority setting for different health services in low- and middle-income countries (LMICs), yet these factors are integral to understanding how national health agendas are established. We investigated factors that facilitate or prevent surgical care from being prioritized in LMICs. METHODS AND FINDINGS: We undertook country case studies in Papua New Guinea, Uganda, and Sierra Leone, using a qualitative process-tracing method. We conducted 74 semi-structured interviews with stakeholders involved in health agenda setting and surgical care in these countries. Interviews were triangulated with published academic literature, country reports, national health plans, and policies. Data were analyzed using a conceptual framework based on four components (actor power, ideas, political contexts, issue characteristics) to assess national factors influencing priority for surgery. Political priority for surgical care in the three countries varies. Priority was highest in Papua New Guinea, where surgical care is firmly embedded within national health plans and receives significant domestic and international resources, and much lower in Uganda and Sierra Leone. Factors influencing whether surgical care was prioritized were the degree of sustained and effective domestic advocacy by the local surgical community, the national political and economic environment in which health policy setting occurs, and the influence of international actors, particularly donors, on national agenda setting. The results from Papua New Guinea show that a strong surgical community can generate priority from the ground up, even where other factors are unfavorable. CONCLUSIONS: National health agenda setting is a complex social and political process. To embed surgical care within national health policy, sustained advocacy efforts, effective framing of the problem and solutions, and country-specific data are required. Political, technical, and financial support from regional and international partners is also important.