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.

The unrestricted global effort to complete the COOL trial.

BACKGROUND: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Abdominal Trauma Imaging in a Nigerian Tertiary Hospital-Our Experience with 87 Adult Patients.

Introduction: Abdominal trauma is a major cause of morbidity and mortality in low- and medium-income countries (LMICs). Abdominal trauma imaging is important in determining the location and severity of organ injury, the need for surgery, and the identification of complications. The choice of imaging in abdominal trauma in LMICs is influenced by peculiar problems, which include the availability of imaging modality, expertise, and cost. There are few reports on options of trauma imaging in LMICs, and this study aimed to identify and characterise the type of imaging done for patients presenting with abdominal trauma at the University of Ilorin Teaching Hospital. Materials and Methods: This was a retrospective observational study of patients with abdominal trauma who presented at the University of Ilorin Teaching Hospital from 2013 to 2019. Records were identified, and data were extracted and analysed. Results: A total of 87 patients were included in the study. There were 73 males and 14 females. The abdominal ultrasound was the commonest modality done in 36 (41%) patients, whereas abdominal computed tomography was done in five (6%) patients. Eleven patients (13%) had no imaging done, and 10 of these patients proceeded to having surgery. In patients with intraoperative finding of perforated viscus, the sensitivity of radiography was 85% and specificity was 100%, whereas that of the ultrasound was 86.7% and 50% for sensitivity and specificity, respectively. The ultrasound scan was the commonest imaging done for patients who presented with features of haemorrhage (P = 0.04), odds ratio (OR) = 1.29 (95% confidence interval [CI] = 1.08-1.6), and patients with severe injury, P = 0.03, OR = 2.07 (95% CI = 1.06-4.06). Gender (P = 0.64), shock at presentation (P = 0.19), and mechanism of injury (P = 0.11) did not influence the choice of imaging. Conclusions: Abdominal trauma imaging in this setting was majorly via ultrasound and abdominal radiographs. Factors suggested to influence the pattern of abdominal trauma imaging in LMICs include the availability of specific imaging modality, cost, lack of standardisation and definite abdominal trauma protocols.

Pattern of Presentation and Outcome of Adult Patients with Abdominal Trauma - A 7-Year Retrospective Study in a Nigerian Tertiary Hospital.

Introduction: Abdominal trauma is a major cause of morbidity and mortality in low- and middle-income countries. There is a paucity of trauma data in this region and this study aimed to show the pattern of presentation and outcome of patients with abdominal trauma at a North-Central Nigerian Teaching Hospital. Methods: This was a retrospective, observational study of patients with abdominal trauma who presented at the University of Ilorin Teaching Hospital from January 2013 to December 2019. Patients with clinical and/or radiological evidence of abdominal trauma were identified, and data extracted and analyzed. Results: A total of 87 patients were included in the study. There were 73 males and 14 females (5.2:1) with a mean age of 34.2 years. Blunt abdominal injury occurred in 53 (61%) patients with 10 patients (11%) having concomitant extra-abdominal injuries. A total of 105 abdominal organ injuries occurred in 87 patients with the small bowel being the most frequently injured organ in penetrating trauma, while in blunt abdominal injury, the spleen was most commonly injured. A total of 70 patients (80.5%) had emergency abdominal surgery with a morbidity rate of 38.6% and negative laparotomy rate of 2.9%. There were 15 deaths in the period accounting for 17% of patients with sepsis as the most common cause of death (66%). Shock at presentation, late presentation >12 h, need for perioperative intensive care unit admission, and repeat surgery were associated with a higher risk of mortality (P < 0.05). Conclusion: Abdominal trauma in this setting is associated with a significant amount of morbidity and mortality. Typical patients present late and with poor physiologic parameters often resulting in an undesirable outcome. There should be steps targeted at preventive policies focused on reducing the incidence of road traffic crashes, terrorism, and violent crimes as well as improving health care infrastructure to cater to this specific group of patients.

Risk Factors, Diagnosis and Management of Chyle Leak Following Esophagectomy for Cancers: An International Consensus Statement.

This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background: Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods: This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results: In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions: Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.

Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

Determinants of late detection and advanced-stage diagnosis of breast cancer in Nigeria.

OBJECTIVE: To describe the risk factors for late detection and advanced-stage diagnosis among patients who detected their BC early. METHOD: Using secondary data, we analyzed the impact of socio-demographic factors, premorbid experience, BC knowledge, and health-seeking pattern on the risk of late detection and advanced-stage diagnosis after early BC detection. Test of statistical significance in SPSS and EasyR was set at 5% using Sign-test, chi-square tests (of independence and goodness of fit), odds ratio, or risk ratio as appropriate. RESULT: Most socio-demographic factors did not affect detection size or risk of disease progression in the 405 records analyzed. High BC knowledge, p-value = 0.001, and practicing breast self-examination (BSE) increased early detection, p-value = 0.04, with a higher probability (OR 1.6 (95% CI 1.1-2.5) of detecting <2cm lesions. Visiting alternative care (RR 1.5(95% CI 1.2-1.9), low BC knowledge (RR 1.3(95% CI 1.1-1.9), and registering concerns for hospital care increased the risk of advanced-stage diagnosis after early detection (64% (95% CI 55-72)). Adhering to the monthly BSE schedule reduced the risk of advanced-stage diagnosis by -25% (95% CI -49, -1.1) in the presence of socioeconomic barriers. CONCLUSION: Strategies to increase BC knowledge and BSE may help BC downstaging, especially among women with common barriers to early diagnosis.

Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review.

BACKGROUND: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. METHODS: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. RESULTS: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. CONCLUSION: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.

The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression.

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

Presentation intervals and the impact of delay on breast cancer progression in a black African population.

BACKGROUND: The help-seeking interval and primary-care interval are points of delays in breast cancer presentation. To inform future intervention targeting early diagnosis of breast cancer, we described the contribution of each interval to the delay and the impact of delay on tumor progression. METHOD: We conducted a multicentered survey from June 2017 to May 2018 hypothesizing that most patients visited the first healthcare provider within 60 days of tumor detection. Inferential statistics were by t-test, chi-square test, and Wilcoxon-Signed Rank test at p-value 0.05 or 95% confidence limits. Time-to-event was by survival method. Multivariate analysis was by logistic regression. RESULTS: Respondents were females between 24 and 95 years (n = 420). Most respondents visited FHP within 60 days of detecting symptoms (230 (60, 95% CI 53-63). Most had long primary-care (237 of 377 (64 95% CI 59-68) and detection-to-specialist (293 (73% (95% CI 68-77)) intervals. The primary care interval (median 106 days, IQR 13-337) was longer than the help-seeking interval (median 42 days, IQR 7-150) Wilcoxon signed-rank test p = 0.001. There was a strong correlation between the length of primary care interval and the detection-to-specialist interval (r = 0.9, 95% CI 0.88-0.92). Patronizing the hospital, receiving the correct advice, and having a big tumor (> 5 cm) were associated with short intervals. Tumors were detected early, but most became advanced before arriving at the specialist clinic. The difference in tumor size between detection and arriving at a specialist clinic was 5.0 ± 4.9 cm (95% CI 4.0-5.0). The hazard of progressing from early to locally advanced disease was least in the first 30 days (3%). The hazard was 31% in 90 days. CONCLUSION: Most respondents presented early to the first healthcare provider, but most arrived late at a specialist clinic. The primary care interval was longer than the help-seeking interval. Most tumors were early at detection but locally advanced before arriving in a specialist clinic. Interventions aiming to shorten the primary care interval will have the most impact on time to breast cancer presentation for specialist oncology care in Nigeria.

Treatment of colorectal cancer in Sub-Saharan Africa: Results from a prospective Nigerian hospital registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Mortality for CRC is improving in high income countries, but in low and middle income countries, rates of disease and death from disease are rising. In Sub-Saharan Africa, the ratio of CRC mortality to incidence is the highest in the world. This study investigated the nature of CRC treatment currently being offered and received in Nigeria. METHODS: Between April 2013 and October 2017, a prospective study of consecutively diagnosed cases of CRC was conducted. Patient demographics, clinical features, and treatment recommended and received was recorded for each case. Patients were followed during the study period every 3 months or until death. RESULTS: Three hundred patients were included in our analysis. Seventy-one percent of patients received a recommended surgical operation. Of those that didn't undergo surgery as recommended, 37% cited cost as the main reason, 30% declined due to personal reasons, and less than 5% absconded or were lost to follow up. Approximately half of patients (50.5%) received a chemotherapy regimen when it was recommended, and 4.1% received radiotherapy when this was advised as optimal treatment. With therapy, the median overall survival for patients diagnosed with stage III and stage IV CRC was 24 and 10.5 months respectively. Overall, we found significantly better median survival for patients that received the recommended treatment (25 vs 7 months; P < .01). CONCLUSIONS: A number of patients were unable to receive the recommended treatment, reflecting some of the burden of untreated CRC in the region. Receiving the recommended treatment was associated with a significant difference in outcome. Improved healthcare financing, literacy, training, access, and a better understanding of tumor biology will be necessary to address this discrepancy.

Is Colorectal Cancer Screening Appropriate in Nigeria?

PURPOSE: The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. METHODS: We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. RESULTS: Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. CONCLUSION: Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.

A symptom-based model to predict colorectal cancer in low-resource countries: Results from a prospective study of patients at high risk for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) rates in low-resource countries, which typically lack CRC screening programs, are rising. This study determined whether a risk model for patients with rectal bleeding could identify patients with curable CRC. METHODS: This prospective, cross-sectional study evaluated a model constructed from data from 1 hospital and validated at 2 other hospitals. The primary endpoint was the ability of the model to predict CRC, as diagnosed by colonoscopy, from clinical characteristics. The secondary endpoint was to determine the percentage of patients who had CRC. RESULTS: Consecutive patients who were 45 years old or older and had self-reported rectal bleeding for more than 1 week were evaluated. From January 2014 to July 2016, 362 patients answered a questionnaire and underwent colonoscopy. In the validation cohort, 56% of patients with rectal bleeding, weight loss, and changes in bowel habits had CRC, whereas 2% of patients with bleeding alone did. Overall, 18.2% of the patients had CRC, and 8.6% had adenomas. The proportion of CRC patients with potentially curable stage II or III disease was 74%, whereas the historical rate was 36%. The combination of rectal bleeding with both symptoms significantly predicted CRC in the validation set (odds ratio, 12.8; 95% confidence interval, 4.6-35.4; P < .001). CONCLUSIONS: In low-resource settings, patients with rectal bleeding, weight loss, and changes in bowel habits should be classified as high risk for CRC. Patients with a high risk score should be prioritized for colonoscopy to increase the number of patients diagnosed with potentially curable CRC. Cancer 2018;124:2766-2773. © 2018 American Cancer Society.

Medical students' perception of objective structured clinical examination: a feedback for process improvement.

BACKGROUND: Medical educators have always been desirous of the best methods for formative and summative evaluation of trainees. The Objective Structured Clinical Examination (OSCE) is an approach for student assessment in which aspects of clinical competence are evaluated in a comprehensive, consistent, and structured manner with close attention to the objectivity of the process. Though popular in most medical schools globally, its use in Nigeria medical schools appears limited. OBJECTIVES: This study was conceived to explore students' perception about the acceptability of OSCE process and to provide feedback to be used to improve the assessment technique. DESIGN: A cross-sectional survey was conducted on final-year medical students, who participated in the final MBBS surgery examination in June 2011. A 19-item self-administered structured questionnaire was employed to obtain relevant data on demographics of respondents and questions evaluating the OSCE stations in terms of the quality of instructions and organization, learning opportunities, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared with other formats. Students' responses were based on a 5-point Likert scales ranging from strongly disagree to strongly agree. The data were analyzed using SPSS, version 15 (SPSS, Inc, Chicago, IL). SETTING: The study took place at the University of Ilorin, College of Health Science. PARTICIPANTS: A total of 187 final-year medical students were enrolled in to the survey. RESULTS: Of 187 eligible students, 151 completed the self-administered questionnaire representing 80.7% response rate. A total of 61 (40.4%) students felt that it was easy to understand written instructions at the OSCE stations. In total, 106 (70.2%) students felt that the time allocated to each station was adequate. A total of 89 (58.9%) students agreed that the OSCE accurately measured their knowledge and skill, and 85 (56.3%) reported that OSCE enhanced their communication skill. Of the respondents, 80 (53%) felt that OSCE caused them to be nervous, and 73 (48.3%) expressed their concern about the interevaluator variability at manned stations. OSCE was perceived to be the second most fair test format by 53 (35.1%) respondents, and 56 (37.1%) also suggested that OSCE needs to be used much more than the other assessment formats. CONCLUSION: The findings in this survey appear reassuring regarding students' perception about the validity, objectivity, comprehensiveness, and overall organization of OSCE in the department of surgery. The need to introduce OSCE early in the surgical curriculum is also underscored. The overall feedback was very useful and will facilitate a critical review of the process.