Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. METHODS: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. DISCUSSION: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. TRIAL REGISTRATION: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

Establishment of an endoscopic retrograde cholangiopancreatography (ERCP) program in rural Kenya: a review of patient and trainee outcomes.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a leading modality for treatment of biliary and pancreatic disease but is not widely available in sub-Saharan Africa. We aimed to assess the development and outcomes of an ERCP service in southwestern Kenya, including case volumes, success rates, infrastructure, and training. METHODS: We conducted a retrospective review of all ERCPs performed at Tenwek Hospital in Bomet, Kenya between January 1, 2011 and March 31, 2020. RESULTS: In total 277 ERCP procedures were attempted during the study period. The commonest indication was obstructive jaundice: 91 patients (32.9%) had malignancy and 85 (30.7%) had choledocholithiasis. Overall clinical success rate was 76.1% and was the highest in patients with biliary stones (81.2%) and lowest in those with tumors (73.5%) (p = 0.094). Procedure-related adverse events occurred in 11.9%, including post-ERCP pancreatitis in 3.6%, with a procedure-related mortality rate of 1.4%. Annual case volumes increased, and mean procedure duration decreased from 162 to 115 min (p = 0.0007) over time. A previously- rained endoscopist initially performed all cases; two staff endoscopists were trained in ERCP during the study period, performing 130 and 89 ERCPs during training, with clinical success rates of 84% and 74% during their subsequent independent practice. CONCLUSION: An ERCP service can be successfully developed at a rural African hospital, with acceptable success and adverse event rates. Biliary obstruction due to stones or tumors are the most common findings. While a previously trained endoscopist should initiate and champion the service, staff endoscopists can be successfully trained despite limited case volumes.

Gastrointestinal endoscopy experience of surgical trainees throughout rural Africa.

BACKGROUND: Gastrointestinal endoscopy (GIE) is not routinely accessible in many parts of rural Africa. As surgical training expands and technology progresses, the capacity to deliver endoscopic care to patients improves. We aimed to describe the current burden of gastrointestinal (GI) disease undergoing GIE by examining the experience of surgical training related to GIE. METHODS: A retrospective review was conducted on GIE procedures performed by trainees with complete case logs during 5-year general surgery training at Pan-African Academy of Christian Surgeons (PAACS) sites. Cases were classified according to diagnosis and/or indication, anatomic location, intervention, adverse events, and outcomes. Comparisons were performed by institutional location and case volumes. Analysis was performed for trainee self-reported autonomy by post-graduate year and case volume experience. RESULTS: Twenty trainees performed a total of 2181 endoscopic procedures. More upper endoscopies (N = 1,853) were performed than lower endoscopies (N = 325). Of all procedures, 546 (26.7%) involved a cancer or mass, 267 (12.2%) involved a report of blood loss, and 452 (20.7%) reported pain as a component of the diagnosis. Interventions beyond biopsy were reported in 555 (25%) procedures. Esophageal indications predominated the upper endoscopies, particularly esophageal cancer. Trainees in high-volume centers and in East Africa performed more interventional endoscopy and procedures focused on esophageal cancer. Procedure logs documented adverse events in 39 cases (1.8% of all procedures), including 16 patients (0.8%) who died within 30 days of the procedure. Self-reported autonomy improved with both increased endoscopy experience and post-graduate year. CONCLUSIONS: GIE is an appropriate component of general surgery residency training in Africa, and adequate training can be provided, particularly in upper GI endoscopy, and includes a wide variety of endoscopic therapeutic interventions.

Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya.

BACKGROUND: Low serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression. RESULTS: The mean serum selenium concentration was 85.5 (±28.3) µg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06-14.19). CONCLUSION: This is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies.

Esophageal Squamous Dysplasia is Common in Asymptomatic Kenyans: A Prospective, Community-Based, Cross-Sectional Study.

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is endemic in east Africa and is a leading cause of cancer death among Kenyans. The asymptomatic precursor lesion of ESCC is esophageal squamous dysplasia (ESD). We aimed to determine the prevalence of ESD in asymptomatic adult residents of southwestern Kenya. METHODS: In this prospective, community-based, cross-sectional study, 305 asymptomatic adult residents completed questionnaires and underwent video endoscopy with Lugol's iodine chromoendoscopy and mucosal biopsy for detection of ESD. RESULTS: Study procedures were well tolerated, and there were no adverse events. The overall prevalence of ESD was 14.4% (95% confidence interval (CI): 10-19%), including 11.5% with low-grade dysplasia and 2.9% with high-grade dysplasia. The prevalence of ESD was >20% among men aged >50 years and women aged >60 years. Residence location was significantly associated with ESD (Zone A adjusted odds ratio (OR) 2.37, 95% CI: 1.06-5.30 and Zone B adjusted OR 2.72, 95% CI: 1.12-6.57, compared with Zone C). Iodine chromoendoscopy with biopsy of unstained lesions was more sensitive than white-light endoscopy or random mucosal biopsy for detection of ESD and had 67% sensitivity and 70% specificity. CONCLUSIONS: ESD is common among asymptomatic residents of southwestern Kenya and is especially prevalent in persons aged >50 years and those living in particular local regions. Lugol's iodine chromoendoscopy is necessary for detection of most ESD but has only moderate sensitivity and specificity in this setting. Screening for ESD is warranted in this high-risk population, and endoscopic screening of Kenyans is feasible, safe, and acceptable, but more accurate and less invasive screening tests are needed.

Randomized Trial of Small-diameter Versus Large-diameter Esophageal Stents for Palliation of Malignant Esophageal Obstruction.

GOALS: To assess the effect of esophageal stent diameter on outcomes of patients with malignant esophageal obstruction. BACKGROUND: Esophageal self-expandable metal stents (SEMS) effectively palliate dysphagia due to malignancy, but the best stent diameter is unknown. STUDY: A prospective randomized trial was conducted at a regional referral hospital. One hundred persons with unresectable esophageal cancer were enrolled, randomized to receive a SEMS of either 18 or 23 mm shaft diameter but identical design, and followed until death. Outcome measurements were dysphagia score, adverse events, endoscopic reintervention, and survival. RESULTS: The study arms were evenly matched. Dysphagia resolved after stent placement in 95% in both groups. After 6 months the cumulative incidence of recurrent dysphagia was 38% (95% CI 18%-53%) versus 47% (26%-63%) in the small-diameter versus large-diameter groups, respectively (P=0.23). The cumulative incidence of adverse events was 57% in both groups at 6 months, with trends toward more frequent gastrointestinal bleeding and esophago-respiratory fistula in the large-diameter group, and more frequent stent migration, stent occlusion, and endoscopic reintervention in the small-diameter group. There was a trend toward longer survival in the small-diameter group (median survival, 5.9 vs. 3 mo; P=0.10). Higher initial performance status score and female gender were associated with improved survival. Limitations include enrollment of only 100 (of a planned 200) persons and incomplete follow-up of some participants. CONCLUSIONS: Small-diameter and large-diameter esophageal SEMS provided similar palliation of dysphagia due to esophageal cancer. The overall incidence of adverse events was not affected by stent diameter, but there was a trend toward longer survival with small-diameter stents (Clinical trial registration number: NCT01894763).

Prevalence of esophageal squamous dysplasia in relatives of patients with esophageal cancer in Southwestern Kenya.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) and its asymptomatic precursor lesion, esophageal squamous dysplasia (ESD), are common in East Africa. It is unknown whether family history of esophageal cancer is a risk factor for both ESD and ESCC in Africa, and whether family members of affected persons should be screened. METHODS: We recruited 296 asymptomatic adult first-degree relatives of ESCC patients residing in southwestern Kenya. Participants completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy to determine the prevalence of ESD. Prevalence comparisons were made with a prior population-based cohort from the same catchment area who also underwent Lugol's chromoendoscopy. RESULTS: Mean age was 40.7 years, compared to 62.7 years in the prior population study. The overall prevalence of ESD/ESCC among first-degree relatives was 14.7%, comparable to the background population prevalence of 14.4%, and this comparability remained even after adjusting for the different age distributions of the studies. Post-primary education was the only measured variable that was associated with a decreased risk of ESD/ESCC (adjusted OR=0.31, 95% CI: 0.11, 0.83). There was heterogeneity in the ESD prevalence across families, even after adjustments for varying age and other measured factors. CONCLUSIONS: The prevalence of esophageal squamous dysplasia among first-degree relatives of persons with ESCC was similar to that of the background population of southwestern Kenya; however, there was heterogeneity in ESD prevalence between families, suggesting other genetic or environmental factors may influence family prevalence. Further study of families with a high prevalence of ESD or ESCC is justified.

Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenya.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot. OBJECTIVE: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions. METHODS: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD. RESULTS: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD. CONCLUSIONS: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.

Investigating tea temperature and content as risk factors for esophageal cancer in an endemic region of Western Kenya: Validation of a questionnaire and analysis of polycyclic aromatic hydrocarbon content.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is common in certain areas worldwide. One area, western Kenya, has a high risk of ESCC, including many young cases (<30 years old), but has limited prior study of potential risk factors. Thermal injury from hot food and beverages and exposure to polycyclic aromatic hydrocarbons (PAHs) have been proposed as important risk factors for ESCC in other settings. The beverage of choice in western Kenya is milky tea (chai). METHODS: Healthy individuals >18 years of age who were accompanying relatives to an endoscopy unit were recruited to participate. The preferred initial temperature of chai consumption in these adults was measured by questionnaire and digital thermometer. Comparisons of these results were assessed by kappa statistics. Concentrations of 26 selected PAHs were determined by gas chromatography/mass spectrometry in samples of 11 brands of commercial tea leaves commonly consumed in Kenya. RESULTS: Kappa values demonstrated moderate agreement between questionnaire responses and measured temperatures. The mean preferred chai temperatures were 72.1 °C overall, 72.6 °C in men (n = 78), and 70.2 °C in women (n = 22; p < 0.05). Chai temperature did not significantly differ by age or ethnic group. The PAH levels in the commercial Kenyan tea leaves were uniformly low (total PAH < 300 ng/g of leaves). CONCLUSIONS: Study participants drink chai at higher temperatures than previously reported in other high-risk ESCC regions. Chai is not, however, a source of significant PAH exposure. Very hot chai consumption should be further evaluated as a risk factor for ESCC in Kenya with the proposed questionnaire.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.