The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of ,, ,, ,, and . Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

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.

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BACKGROUND Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The incidence of TBI in low- and middle-income countries (LMICs) is disproportionately high, with an associated increased risk of mortality from TBI relative to high-income countries. Although computed tomography is the diagnostic method of choice, this is often unavailable in LMICs. Exploratory burr holes may provide a suitable choice for diagnosis and treatment of TBI. METHODS We performed a retrospective review of prospectively collected data at KCH, a tertiary care center in Lilongwe, Malawi. All trauma patients presenting between June 2012 and July 2015 with a deteriorating level of consciousness and localizing signs and who underwent exploratory burr holes were included. Additionally, we included all patients admitted with TBI, requiring higher-level care during 2011. No patients underwent exploratory burr hole during this time. We performed logistic regression to identify predictors of mortality in the total population of TBI patients. RESULTS Among the 241 patients who presented to KCH with TBI requiring higher-level care, the total mortality was 16.4%. More than half (163, or 68%) underwent exploratory burr hole with a mortality of 6.8%. Mortality in patients who did not undergo exploratory burr hole was 43.9%. Upon adjusted logistic regression, not undergoing exploratory burr hole significantly increased the odds of mortality (odds ratio = 12.0, P = 0.000, 95% confidence interval = 4.48–31.9). CONCLUSION Exploratory burr holes remain an important diagnostic and therapeutic procedure for TBI in LMICs. Exploratory burr hole technique should be integrated into general surgery education to attenuate TBI-related mortality.

IntroductionPeritonitis is a life-threatening condition with a multitude of etiologies that can vary with geographic location. The aims of this study were to elucidate the etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi.MethodsAll patients admitted to Kamuzu Central Hospital (KCH) who underwent an operation for treatment of peritonitis during the calendar year 2008 were eligible. Peritonitis was defined as abdominal rigidity, rebound tenderness, and/or guarding in one or more abdominal quadrants. Subjects were identified from a review of the medical records for all patients admitted to the adult general surgical ward and the operative log book. Those who met the definition of peritonitis and underwent celiotomy were included.Results190 subjects were identified. The most common etiologies were appendicitis (22%), intestinal volvulus (17%), perforated peptic ulcer (11%) and small bowel perforation (11%). The overall mortality rate associated with peritonitis was 15%, with the highest mortality rates observed in solid organ rupture (35%), perforated peptic ulcer (33%), primary/idiopathic peritonitis (27%), tubo-ovarian abscess (20%) and small bowel perforation (15%). Factors associated with death included abdominal rigidity, generalized (versus localized) peritonitis, hypotension, tachycardia and anemia (p < 0.05). Age, gender, symptoms (obstipation, vomiting) and symptom duration, tachypnea, abnormal temperature, leukocytosis, hemoconcentration, thrombocytopenia and thrombocytosis were not associated with mortality (p = NS).ConclusionsThere are several signs and laboratory findings predictive of poor outcome in Malawian patients with peritonitis. Tachycardia, hypotension, anemia, abdominal rigidity and generalized peritonitis are the most predictive of death (P < 0.05 for each). Similar to studies from other African countries, in our population the most common cause of peritonitis was appendicitis, and the overall mortality rate among all patients with peritonitis was 15%. Identified geographical differences included intestinal volvulus, rare in the US but the 2nd most common cause of peritonitis in Malawi and gallbladder disease, common in Ethiopia but not observed in Malawi. Future research should investigate whether correction of factors associated with mortality might improve outcomes.

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Summary INTRODUCTION Non-communicable diseases including surgical conditions are gaining attention in developing countries. Despite this there are few metrics for surgical capacity. We hypothesized that (a) the ratio of emergent to total hernia repairs (E/TH) would correlate with per capita health care expenditures for any given country, and (b) the E/TH is easy to obtain in resource-poor settings. METHODS We performed a systematic review to identify the E/TH for as many countries as possible (Prospero registry CRD42013004645). We screened 1285 English language publications since 1990; 23 met inclusion criteria. Primary data was also collected from Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. A total of 13 countries were represented. Regression analysis was used to determine the correlation between per capita healthcare spending and the E/TH. RESULTS There is a strong correlation between the log values of the ratio emergent to total groin hernias and the per capita health care spending that is robust across country income levels (R2=0·823). Primary data from KCH was easily obtained and demonstrated a similar correlation. CONCLUSIONS The ratio of emergent to total groin hernias is a potential measure of surgical capacity using data that is easily attainable. Further studies should validate this metric against other accepted health care capacity indicators.