Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality worldwide, and there are limited molecular screening options. Following a prior discovery and validation studies in subjects from the United States, China, and Iran, we aimed to validate methylated DNA markers (MDM) for ESCC detection in Malawi, a country with one of the highest ESCC incidence. Fourteen MDMs were tested on 177 tissue samples. Ten MDMs showed excellent performance (AUCs ≥ 0.85); a random forest model achieved an AUC of 0.97. The consistent cross-population performance suggests potential for universal application of these MDMs and further justifies exploring nonendoscopic sampling methods, such as swallowed cell collection devices in combination with MDMs, for efficient and cost-effective screening in high-incidence populations. PREVENTION RELEVANCE:This study validates MDMs for early detection of ESCC in Malawi, supporting their potential role in noninvasive, population-based screening strategies in Africa to enable early detection and timely intervention for cancer interception, potentially reducing cancer burden in high-incidence, resource-limited regions.

Supplementary Figure S2. Expression of Mutsig CV genes in cohorts from Tanzania (Panel A) and Malawi (Panel B).

BACKGROUND: Esophageal cancer (EC) is the third leading cause of cancer-related morbidity and mortality in Malawi. Given limited imaging capacity and high costs, staging is not routinely performed. One proposed staging algorithm is to first evaluate for metastatic disease using low-cost chest radiography (CXR) and abdominal ultrasound (US) followed by confirmatory computerized tomography (CT) of the chest and abdomen if no metastases identified on initial screening. The feasibility of this approach is unknown for EC in sub–Saharan Africa and was studied in the context of a larger prospective observational cohort study of EC in Malawi. METHODS: From 2021 to 2022, EC patients at Kamuzu Central Hospital in Lilongwe, Malawi enrolled in the Treatment Outcomes of Esophageal Cancer in Malawi (TOEC-M) study were recruited. Participants were scheduled for a CXR, US, and CT scan as part of this sub-study. Participant characteristics, completion rates, imaging findings, and barriers to completion were documented. For participants undergoing all three imaging studies, sensitivity and specificity were calculated. RESULTS: Of 150 patients in TOEC-M, 67 (44.7%) enrolled in this sub-study. Mean age was 55.4 years and 50.8% were males. The majority had mid-esophageal (38 [56.7%]) squamous cell carcinomas (54 [80.6%]). CXR was completed in 54 (80.6%) study participants, US in 43 (64.2%), CT chest in 29 (43.3%), and CT abdomen in 24 (35.8%). Sixteen (23.9%) completed all studies and 4 (6.0%) did not undergo any imaging. Of the 63 patients that were imaged, metastatic disease was identified in 18 (28.6%) by any modality. Positive findings were identified on 3 (5.6%) CXRs, 4 (9.3%) US, and 18 (62.1%) CTs, most frequently liver masses followed by lung nodules and adenopathy. Barriers to imaging completion included participant functional status and scanner availability. CONCLUSIONS: As access to EC treatment modalities expands, feasible and accurate staging will become increasingly important to guide clinical management. Our results suggest that CXR and US may serve as useful initial tools for assessing metastatic disease. In patients not medically fit for oncologic treatment, positive findings on CXR and US may allow CT to be deferred. Barriers to implementation of a pragmatic stepwise staging algorithm identified in this study can inform future research and care for patients with EC in similar resource-limited settings.

Supplementary Figure S1. Measurement of RNA Quantity and Quality using PAXgene tissue container vs. RNAlater.

PURPOSEEsophageal squamous cell carcinoma (ESCC) is a prevalent cancer in eastern Africa. Optimal management strategies in eastern Africa have not been well established. This study aimed to evaluate ESCC treatment outcomes at Kamuzu Central Hospital (KCH), a national cancer center in Malawi.METHODSThis prospective, observational, cohort study was conducted as part of a multicenter collaboration within the African Esophageal Cancer Consortium (ClinicalTrials.gov identifier: NCT05177393). Patients who presented to KCH with esophageal cancer (EC) were recruited from June 2021 to December 2022. Data on patient and treatment characteristics were collected using interviews and chart review. Mobile phone outreach was used to assess patient-reported outcomes (PROs). PROs were analyzed using linear mixed modeling. Kaplan-Meier method with log-rank test and Cox proportional hazards regression were used to evaluate overall survival by treatment group.RESULTSA total of 148 of 150 eligible patients enrolled. Of 114 with biopsy-proven EC, 97% (n = 111) had ESCC. Most were documented as having localized disease; however, 56% did not complete staging imaging. Forty-seven percent received supportive care, 30% self-expandable metallic stent (SEMS), 20% chemotherapy, and 3% SEMS plus chemotherapy. SEMS was associated with the highest proportion experiencing dysphagia improvement (SEMS 68% v chemotherapy 63% v supportive care 39%). Twelve-month survival rate was the highest in the chemotherapy arm (29% v supportive care 19% v SEMS 6%, log-rank P = .018).CONCLUSIONESCC remains a highly fatal malignancy in Malawi. Most patients at KCH are treated with SEMS or supportive care. Although data must be interpreted with caution given likely confounding, chemotherapy was associated with the highest 12-month survival rate as compared with SEMS and supportive care, whereas SEMS was associated with the highest likelihood of improved dysphagia.

Introduction Same-day surgical case cancellation consumes resources, disrupts patient care, and has a global prevalence of 18%. A retrospective analysis found that 44% of scheduled elective surgeries were canceled at a public tertiary hospital in Lilongwe, Malawi. To better characterize these cancellations, this study defines a process map for surgical case completion and investigates hospital staff and patient perspectives on contributing factors and burdens of cancellation. Methods We conducted participatory process mapping and in-depth interviews with hospital staff (n = 23) and patients (n = 10) to detail perioperative processes and perspectives on cancellations. We used purposive sampling to recruit staff by hospital role and patients whose surgery had been canceled. Interviews were audio-recorded, translated, and transcribed for process mapping accuracy and thematic analysis using the constant comparative method and NVivo software. Results Staff delineated specific steps of the perioperative process, generating a process map that identifies inefficiencies and opportunities for intervention. Hospital staff described unavoidable causes of case cancellation, such as unreliable water supply and material shortages. Modifiable causes linked to wasted time and resources were also evident, such as chronic tardiness, communication barriers, and inadequate preoperative assessment. Thematic analysis of perceived impacts of cancellation revealed compromised provider-patient relationships, communication breakdown, and emotional distress. Staff and patients expressed frustration, embarrassment, fear, and demoralization when planned surgeries were canceled. Conclusions We demonstrate the use of process mapping as a tool to identify implementation targets for reducing case cancellation rates. Hospital systems can adapt this approach to address surgical case cancellation in their specific setting.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

ObjectiveAlcohol or drug impairment is a major risk factor for road traffic crashes, and studies on this issue are essential to provide evidence-based data for policymakers. In low- and middle-income countries (LMICs), such studies are often conducted in partnership with one or more organizations in high-income countries (HICs). The aim of this article is to provide recommendations for improving project planning and decision-making processes in epidemiological studies on alcohol, drug and traffic safety in LMICs involving HICs.MethodsWe searched Pubmed, Google Scholar, and Google Search for articles and reports in English about lessons learned when conducting collaborative research in LMIC as well as papers presenting recommendations for effective research collaboration with partners in LMICs.ResultsBased on the search results, we selected 200 papers for full text examination. Few were related to studies on the effect of alcohol or drug use on road traffic safety. However, several conclusions and recommendations from other studies were found to be relevant. We combined the findings with our own experience in a narrative review. We also present a checklist for risk and quality assessment.ConclusionsMany papers presented similar recommendations, which included the importance of addressing local needs, ensuring adequate resources, local project ownership and leadership, establishing strong partnerships among all involved stakeholders, promoting shared decision-making and planning, and implementing strategies to translate research findings into policy, practice, and publications. It is also important to avoid HIC bias, which prioritizes the interests or perspectives of HICs over those of LMICs.

BACKGROUND:Same-day cancellation of surgery affects up to 44% of cases at a public tertiary hospital in Lilongwe, Malawi. To characterize these cancellations, this study examines surgical volume, cancellation causes, and surgery completion rate after initial cancellation, which are not otherwise monitored for analysis in this setting. METHODS:We conducted a serial cross-sectional study at the Kamuzu Central Hospital (KCH) during a 6 month period. Variables included patient demographics, procedure information, and hospital capacity factors. Bivariate and multivariable regression models were constructed to assess factors associated with cancellation. RESULTS:Of the 3121 total surgeries, 2626 (84.1%) were elective procedures, of which 747 (28.4%) were canceled. Orthopedic surgery observed the highest cancellation rate (36.5%). Process-related factors, such as starting cases late, were the primary reason for cancellation (64.3%). Only 40% of patients with a canceled surgery underwent their procedure after index admission, with a median wait time of 3 days. Emergency cases (aOR: 0.50 and CI: 0.39 and 0.64) and first cases of the day (aOR: 0.02 and CI: 0.01 and 0.04) were associated with lower odds of cancellation. Facility factors associated with lower odds of cancellation included number of open operating rooms (OR: 0.86 and CI: 0.77 and 0.96) and anesthetists assigned on duty (OR: 0.94 and CI: 0.88 and 0.99). CONCLUSION:Cancellation of elective surgery was primarily driven by process-related factors. We identify facility-related factors associated with lower odds of cancellation and thus provide targets for future interventions at KCH. Studies examining patient outcomes following elective case cancellation are warranted as most patients never return for surgery following cancellation.

PURPOSEEsophageal cancer (EC) is the second most common cancer in Malawi, with esophageal squamous cell carcinoma (ESCC) representing >90% of all ECs. Despite significant morbidity and mortality, little is known about disease outcomes. In this study, we assess survival after ESCC diagnosis in Malawi.METHODSWe report on ESCC cases enrolled in a case-control study at Kamuzu Central Hospital in Lilongwe from August 2017 to April 2020. Suspected cases completed a questionnaire interview; provided blood, urine, and saliva specimens; and underwent a tumor biopsy for histologic confirmation. Cases were followed up by phone biweekly from enrollment to the study end date (December 31, 2020), date of death, or loss to follow-up. Survival was assessed using Kaplan-Meier analysis with the log-rank test. We also examined associations between treatment and ESCC mortality using Cox regression models.RESULTSThere were 300 patients with ESCC enrolled in this study, of whom 290 (97%) had known vital status at the end of follow-up and 10 (3%) were lost to follow-up. Among the 290 patients, 282 (97%) died during follow-up. The median age at enrollment was 55 years (IQR, 48-66), and the median time to death was 106 days (95% CI, 92 to 127). The 1-year, 2-year, and 3-year survival rates were 11% (95% CI, 8 to 15), 3% (95% CI, 1 to 6), and 0.9% (95% CI, 0.8 to 4), respectively. Palliative chemotherapy significantly improved the overall survival of patients with ESCC (Plog-rank = .038) and was significantly associated with reduced mortality (adjusted hazard ratio, 0.71 [95% CI, 0.51 to 0.99]). No significant association was observed between tobacco use, alcohol consumption, or HIV status and mortality.CONCLUSIONSurvival after diagnosis of ESCC was poor in Malawi. Although palliative chemotherapy was associated with improved survival, prevention and earlier detection remain key priorities to improve ESCC mortality at a population level.

Sex disparities in access to health care in low-resource settings have been demonstrated. Still, there has been little research on the effect of sex on postoperative outcomes. We evaluated the relationship between sex and mortality after emergency abdominal surgery. We performed a retrospective cohort study using the acute care surgery database at Kamuzu Central Hospital (KCH) in Malawi. We included patients who underwent emergency abdominal surgery between 2013 and 2021. We created a propensity score weighted Cox proportional hazards model to assess the relationship between sex and inpatient survival. We included 2052 patients in the study, and 76

AbstractBackground: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC. Methods: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA). Results: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort. Conclusions: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites. Impact: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.

Objective Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. Methods We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. Results During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4–4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8–9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3–6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1–2.5 p = 0.021). Conclusion Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Trauma is a leading cause of death and disability worldwide and disproportionately affects those in low- and middle-income countries (LMICs). Globally, two-thirds of injured patients sustain trauma to the thoracic cavity. Further research, capacity building, and increased awareness are needed to limit the high thoracic trauma-associated morbidity and mortality in LMICs.

Background Tracheostomy alone, without mechanical ventilation, has been advocated to maintain a free airway in patients with traumatic brain injury in low-income settings with minimal critical care capacity. However, no reports exist on the outcomes of this strategy. We examine the results of this practice at a central hospital in Malawi. Methods This is a retrospective review of medical records and prospectively gathered trauma surveillance data of patients admitted to Kamuzu Central Hospital, with traumatic brain injury from January 2010 to December 2015. In-hospital mortality rates were examined according to registered traumatic brain injury severity and airway management. Results In our analysis, 1875 of 2051 registered traumatic brain injury patients were included; 83.3% were male, mean age 32.6 (SD 12.9) years. 14.2% (n=267) of the patients had invasive airway management (endotracheal tube or tracheostomy) with or without mechanical ventilation. Mortality in severe traumatic brain injury treated with tracheostomy without mechanical ventilation was 42% (10/24) compared to 21% (14/68) in patients treated without intubation or tracheostomy (p= 0.043). Tracheostomies had an overall complication rate of 11%. Conclusion Tracheostomy without mechanical ventilation in severe traumatic brain injury did not improve survival outcomes in our setting. Tracheostomy for severe traumatic brain injury cannot be recommended when mechanical ventilation is not available unless there are sufficient specialized human resources for follow up in the ward. Efforts to improve critical care facilities and human resource capacity to allow proper use of mechanical ventilation in severe traumatic brain injury should be a high priority in low-income countries where the burden of trauma is high.

In low-income countries (LICs), patients with abdominal surgical emergencies often initially present to primary or district hospitals and are transferred to referral hospitals for surgical management. The transfer process introduces a delay to care, but the relationship between transfer time and outcomes has not been studied in LICs. We sought to evaluate the effect of transfer delays on postoperative outcomes among patients undergoing emergency abdominal surgery in Malawi. This is a retrospective analysis of the acute care surgery database at Kamuzu Central Hospital (KCH), a referral hospital in Malawi. Patients were eligible for inclusion if transferred from another facility to KCH for emergency abdominal surgery. We used logistic regression modeling to evaluate the relationship between transfer time and postoperative complications and mortality. The study included 2037 patients. Female patients, patients transferred from district hospitals, and patients with bowel obstructions were most likely to spend over three days at a referring facility before transfer. On regression modeling, each additional day until transfer was associated with an 18% increase in odds of developing a postoperative complication (OR 1.18, 95% CI 1.05–1.31, p = 0.005) and a 19% increase in odds of postoperative mortality (OR 1.19, 95% CI 1.08–1.31, p < 0.001). Among patients requiring emergency abdominal surgery in Malawi, transfer delays are associated with higher postoperative complications and mortality rates. Further research should focus on identifying the factors causing delays so that interventions aimed at improving the transfer process can be developed.

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 .