Short term micronutrient-antioxidant supplementation has no impact on a serological marker of gastric atrophy in Zambian adults: retrospective analysis of a randomised controlled trial

BACKGROUND: Gastric cancer is a major contributor to cancer deaths in Zambia but, as elsewhere, no preventive strategies have been identified. We set out to investigate the possibility of reducing gastric atrophy, a premalignant lesion, using micronutrient-antioxidant supplementation. METHODS: We analysed 215 archival samples from a randomised controlled trial of micronutrient-antioxidant supplementation carried out from 2003 to 2006. Participants were randomised to receive either the supplement or placebo and had been taking the allocated intervention for a mean of 18 (range 14–27) months when the samples used in this study were taken. We used low pepsinogen 1 to 2 (PEP1:2) ratio as a surrogate marker of gastric atrophy. A PEP 1:2 ratio of less than three was considered low. HIV serology, age, nutritional status, smoking, alcohol intake and gastric pH were also analysed. Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee (011-04-12). The randomized trial was registered (ISRCTN31173864). RESULTS: The overall prevalence of low PEP 1:2 ratio was 15/215 (7%) and it did not differ between the placebo (8/103, 7.8%) and micronutrient groups (7/112, 6.3%; HR 1.24; 95% CI 0.47-3.3; P = 0.79). The presence of low PEP 1:2 ratio was not influenced by HIV infection (HR 1.07; 95% CI 0.37-3.2; P =0.89) or nutritional status but it inversely correlated with gastric pH (Spearman’s rho = -0.34; P = 0.0001). Age above 40 years was associated with atrophy, but neither alcohol nor smoking had any influence. CONCLUSION: Short term micronutrient supplementation does not have any impact on PEP 1:2 ratio, a serological marker of gastric atrophy. PEP 1:2 ratio inversely correlates with gastric pH

Histopathological characterization of lung tumours at the University Teaching Hospital, Lusaka, Zambia: a pilot study

Background: There are limited data on histological classification of primary lung cancer from sub-Saharan Africa. Furthermore, the time trends of age-truncated incidence rates of lung cancer by histological phenotype in Zambia are also unknown. Objectives: The objective of this study was to determine histological types of lung tumours at the University Teaching Hospital (UTH) in Lusaka, Zambia. Methods: This was a retrospective pilot study of lung tumour biopsies collected from the histopathology laboratory at the UTH over a period of one year. Tissue sections were stained and when seen, lung cancer was classified using standard histological methods. Data were analysed using IBM SSPS version 23. Results: A total of 23 lung cancer tissues were retrieved. Histological types included eleven (47.8%) squamous cell carcinoma (SCC), six (26.1%) adenocarcinoma, two (8.7%) small cell carcinoma, two (8.7%) large cell carcinoma, 1 (4.3%) inflammatory myofibroblastic tumours and 1 (4.3%) pleural pulmonary blastoma. The results showed that the most affected age group was 60-69 years with most of the histological subtype in this age group being SCC. There was no statistically significant difference of histological subtypes across age groups, p=0.12. Conclusion: This study has shown that the most commonly diagnosed type of primary lung cancer is squamous cell carcinoma.More data are needed to further corroborate this observation. Keywords: Lung cancer; histopathology; Zambia

A seven-year retrospective review of colonoscopy records from a single centre in Zambia

IntroductionColorectal disease is common throughout the world, but the spectrum of diagnoses across Africa remains largely unexplored. There is anecdotal evidence of changing colorectal disease but this has not been systematically investigated. The aim of this study was to enhance our insight into the spectrum of colonoscopic diagnoses in Zambia.MethodsWe retrieved written colonoscopy reports from January 2008 to December 2015. Collected data were coded by experienced endoscopists and analysed by age, sex, referral source, indication and diagnosis. ResultsIncluded in this analysis were 573 colonoscopy reports. The most common diagnosis was haemorrhoids (n=151, 26%), followed by tumours (n=96,17%). Over this time period, the proportion of normal colonoscopies decreased by 32% (P<0.001), presumably due to introduction of screening of all requests, while the rate of polyp detection increased from 5% to 10% (P=0.006). The detection of polyps was highest in patients less than 16 years (OR 8.4; 95% CI 2.4-26.2, P<0.001). Of those with colorectal tumours, 33/96 (35%) were less than 45 years although the occurrence was higher with advancing age (P=0.02). Diverticular disease was more common in older age groups (median (IQR) age 70 (60-75) years, versus 47 (34-62) years for those without the disease; P=0.0001).ConclusionThis audit has shown that more than a third of colorectal tumours seen during colonoscopy are in patients below the age of 45 years, with the occurrence of polyps being highest in those below 16 years. Diverticular disease is most common in older age groups

Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a case-control study study

Introduction: Gastric cancer is one of the major causes of cancer related deaths, but data from sub-Saharan Africa are very scanty. The cancer genome atlas (TCGA) initiative confirmed Epstein-Barr virus (EBV) related cancer as a distinct subtype, and we set out to look for serological evidence of its role in a sub-Saharan African patient group. Methods: We used stored serum samples obtained from a gastric cancer case-control study conducted between 2010 and 2012 in Lusaka, Zambia. A total of 147 patients were included with 51 gastric adenocarcinoma cases and 96 age and sex matched controls. The presence of antibodies to EBV nuclear antigen-1 (EBNA-1) and early antigen (EA) was determined using commercially available ELISA kits. Data were analysed in STATA Stata Corp, College Station TX. Results: Over 90% of all the samples analysed were positive for antibodies to EBNA-1. The presence of antibodies to EBV EA was significantly higher in gastric cancer cases than in controls, (OR 4.38; 95% CI 1.53-13.06, P=0.0027), with an attributable risk of 23%. HIV infection was also associated with EBV EA seroprevalence (OR 10.97; 95% CI 2.26 -13.06, P=0.001) but not EBNA-1 (OR 0.81; 95% CI 0.10 -38.75, P=0.596). There was no association of EBV infection with age below 45 years, Helicobacter pylori infection, intestinal metaplasia, gastric atrophy or inflammation. Conclusion: We therefore conclude that EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.Pan African Medical Journal 2016; 2

Human epidermal growth factor receptor 2 overexpression in gastric and gastroesophageal junction adenocarcinoma in patients seen at the University Teaching Hospital, Lusaka, Zambia

Background: There are scanty data on the occurrence of gastric tumours overexpressing human epidermal growth factor receptor 2 (HER2) in Africa. Objective: To assess HER2 protein overexpression in gastric and gastroesophageal junction adenocarcinoma (GGEAC) samples from a single centre in Zambia. Methodology: This was a cross-sectional study of formalin-fixed paraffin-embedded blocks with GGEAC. Prepared slides were first stained with Haematoxylin and Eosin and then evaluated for HER2 protein overexpression by immunohistochemistry. Results: A total of 57 gastric tissues were stained and evaluated for HER2 overexpression. Thirteen (23%) showed overexpression, 41/57 (72%) had negative and 3/57 (5%) had equivocal staining. The equivocal cases were excluded from the final analysis. Of the remaining 54 tissues, 28 (52%) were from females, and 26 (48%) were from males. The mean age was 59 years (SD 15 years). HER2 overexpression was highest in moderately differentiated tumours (p=0.0005). Intestinal type tumours had a higher occurrenc of HER2 overexpression than diffuse or mixed sub-types (p=0.0087). HER2 overexpression was not associated with age (p=0.27), sex (p=1.00) or anatomical location (p=1.00). Conclusion: The occurrence of GGEAC HER2 overexpression in Zambian patients is similar to proportions reported elsewhere, and it is associated with moderately differentiated tumours of the intestinal type

Epithelial abnormalities in the small intestine of Zambian children with stunting

BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy. RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE. CONCLUSION: Epithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation

Esophageal squamous cell cancer in a highly endemic region

AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α). METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine. RESULTS: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014). CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not

Trends in upper gastrointestinal diagnosis over four decades in Lusaka, Zambia: a retrospective analysis of endoscopic findings

BACKGROUND AND AIMS: There a shortage of robust information about profiles of gastrointestinal disease in sub-Saharan Africa. The endoscopy unit of the University Teaching Hospital in Lusaka has been running without interruption since 1977 and this 38-year record is largely intact. We report an analysis of endoscopic findings over this period. METHODS: Written endoscopy records from 29th September 1977 to 16th December 2014 were recovered, computerised, coded by two experienced endoscopists and analysed. Temporal trends were analysed using tables, graphs, and unconditional logistic regression, with age, sex of patient, decade, and endoscopist as independent variables to adjust for inter-observer variation. RESULTS: Sixteen thousand nine hundred fifty-three records were identified and analysed. Diagnosis of gastric ulcer rose by 22 %, and that of duodenal ulcer fell by 14 % per decade. Endoscopically diagnosed oesophageal cancer increased by 32 % per decade, but gastric cancer rose only in patients under 60 years of age (21 % per decade). Oesophageal varices were the commonest finding in patients presenting with haematemesis, increasing by 14 % per decade in that patient group. Two HIV-related diagnoses, oesophageal candidiasis and Kaposi’s sarcoma, rose from almost zero to very high levels in the 1990s but fell substantially after 2005 when anti-retroviral therapy became widely available. CONCLUSIONS: This useful dataset suggests that there are important trends in some endoscopic findings over four decades. These trends are not explained by inter-observer variation. Reasons for the divergent trends in incidence of peptic ulceration and apparent trends in diagnosis of upper gastrointestinal cancers merit further exploration

Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial

We thank the Wellcome Trust through the Southern Africa Consortium for Research Excellence for funding this study (WT087537MA)

Introducing the Sanguis-Filum for Detection of Gastric Mucosal Lesions Prior to Endoscopy: A Study Protocol

Early diagnosis of gastric cancer (GC) is compromised by a lack of specific signs to enable identification of affected individuals. We designed the Sanguis-filum (S-filum) as a simple bedside tool that could be used to detect the presence of gastric mucosal lesions prior to endoscopy. We previously published evidence that at a sensitivity of 91%, the presence of free blood in the stomach was associated with mucosal lesions. The S-filum is made of an inert but absorbent string coiled up in a gelatin capsule (Capsuline, FL, USA), which can be swallowed and the string retrieved to test for free blood. Preliminary testing of the S-filum was successfully conducted on healthy volunteers. We now intend to test it on actual patients, comparing the results to oesophagogastroduodenoscopy (OGD) findings. This will enable us to determine the diagnostic accuracy of the S-filum at detecting GC and other mucosal lesions. The S-filum as a bedside tool has the potential to assist healthcare providers to identify individuals likely to have early gastric mucosal lesions and requiring OGD examination. The S-filum could, in the long run, facilitate population-wide screening for early GC prior to endoscopy