African Health Sciences Vol 8 No 2 June 2008
Factors associated with carcinoma of the oesophagus at Mulago
Ponsiano Ocama,1 Magid M Kagimu,1 Michael Odida,2 Henry Wabinga,2 Christopher K Opio,1 Britt
Colebunders,3 Sabrina van Ierssel,3 Robert Colebunders3
1 Department of Medicine, Makerere University, 2 Department of Pathology, Makerere University, 3 University of
Background: In Uganda, as in many other parts of the world cancer of the oesophagus (CAE) is on the rise. Squamous cell carcinoma
and adenocarcinoma are the common subtypes. Risk factors for this cancer have been identified but not studied systematically in
Uganda. Identification of these factors would enable establishment of preventive measures.
Objective To determine the prevalence, histological features and associated factors for CAE among patients referred to the endoscopic
unit of Mulago hospital, Kampala, Uganda.
Methods: We performed a 1-year cross-sectional study in 2004 and 2005 of all patients presenting for oesophageal-gastro-duodenoscopy
(EGD) at Mulago Hospital. Demographic characteristics, behavioural practices, endoscopy findings and histology results where
biopsies were performed were collected using a study tool. Data analysis was done using STATA 8® statistical package
Results: Two hundred nineteen patients were enrolled in the study, three were excluded because they could not tolerate the
endoscopy procedure. Fifty five (19%) of the 287 had histologically proven CAE. Squamous cell carcinoma was found in 100% of
tumours of the upper third, 91% middle third, and 73% lower third of the oesophagus. Four patients had a histological diagnosis of
adenocarcinoma of the oesophagus. Factors that were associated with CAE included age (OR 1.63, CI 1.34-1.98, p value <0.001),
smoking (OR 3.63, CI 1.82-7.23, p value <0.001) and gender (OR 2.17, CI 1.07-4.41, p value 0.032).
Conclusion: Many patients referred for EGD in Uganda had esophageal cancer most of which were.squamous cell type. Smoking,
male gender and older age were risk factors. Preventive measures should target stopping smoking.
African Health Sciences 2008; 8(2): 80-84
Infectious Diseases Institute, Kampala, Uganda
P.O.Box 22418, Kampala
Tel: 256 414 307 224
Fax: 216 414 307 290
Cancer of the oesophagus (CAE) is generally on the
increase worldwide1. Adenocarcinoma of the
oesophagus is increasing at a faster rate now surpassing
squamous cell carcinoma, reversing the trend that had
been seen in the 1970s when the latter was the most
common CAE. 1,2 In Uganda, the incidence of CAE is
also on the rise. 3
Treatment of cancer of the oesophagus is
problematic and mortality rates are very high with no
cure in the majority of cases. Unlike in the West where
treatment trials are on-going in Uganda, only palliative
care can be offered and mortality is almost 100% within
6 months of diagnosis.
CAE can occur at any site of the oesophagus, but
its distribution has not been uniform for all the
histological types. Cancers in the upper one-third of the
oesophagus are mainly of the squamous type while those
of the lower one third are generally adenocarcinoma; in
the middle third of the oesophagus either
adenocarcinoma or squamous cell carcinoma can be
Squamous cell carcinoma of the oesophagus occur more
often in patients with a long standing exposure to tobacco
and alcohol4,5, achalasia6, tylosis7, lye ingestion 8 and celiac
sprue.9 The etiological role of the Human Papilloma
Virus in squamous cell carcinomas is still being
investigated. 10-11 In Uganda, Human Papilloma Virus has
been implicated in squamous cell carcinoma not only of
the cervix but also of the conjunctiva. 12
Oesophageal adenocarcinoma has been
associated with gastro-oesophageal reflux disease13-17 and
a 0.5% annual risk of developing adenocarcinoma has
been reported in patients with Barrett’s esophagus. 18
Previous studies about CAE in Uganda were
done based on data obtained from the cancer registry
and all the tissues studied originated from one county in
the country. 3
This is the first cross-sectional study reporting
the prevalence and factors associated with CAE among
patients referred to an esophageal-gastro-duodenoscopy
(EGD) unit in a Ugandan hospital (Mulago hospital, the
African Health Sciences Vol 8 No 2 June 2008
national referral hospital). Patients from various hospitals
and clinics around the country are referred to this unit.
Various risk factors for CAE have been
identified but these factors have not been studied
systematically in Uganda. Identification of these factors
will enable establishment of preventive measures for
this almost universally fatal cancer which has no effective
Patients and Methods
From September 2004 to September 2005 we performed
a 1-year cross sectional study of all patients presenting
for EGD at Mulago Hospital, Patients were enrolled
after informed consent was obtained, if they were more
then 18 years old, and if there were no contra-indications
for EGD or biopsies.
Data about patient demographics, reason for
referral, possible risk factors for CAE, details of
endoscopic findings, and histology of the CAE were
A CAE was defined when there was endoscopic evidence
of tumour growth arising from the oesophagus with
histological evidence of malignant cells on microscopy.
EGD was performed using a Fujinon
endoscope. Lidocaine 2% spray was applied to provide
local anaesthesia. For patients with suspicious lesions,
the anatomical site of the lesions was described and
biopsies obtained with a forceps device passed through
the working channel of the endoscope. Eight biopsy
tissues of each lesion were taken, fixed in 10% formal
saline solution, appropriately labelled, then dispatched
for evaluation by the pathologist. In those patients in
whom it was possible to pass the endoscope through
the oesophageal stricture caused by the tumour, the
mucosa of the stomach and duodenum were inspected
and additional biopsies were taken if lesions were
Biopsy tissues were embedded in paraffin wax
before they were sliced by microtome to the appropriate
size. The samples were then stained with haematoxylin
and eosin. All biopsies were examined by any one of two
senior pathologists of Makerere University.
Data were entered into Microsoft excel spread
sheets, coded and later exported to STATA 8® statistical
package. The degree of association was determined by
Mann-Whitney test for continuous variables and Fisher’s
exact test for categorical variables.
Risk factors for CAE were identified by
univariate logistic regression. Factors significant at the
5% level were selected in a multivariate logistic
regression model to identify independently significant
Faculty Institutional review board authorization
was obtained from Makerere University Faculty of
Medicine before commencement of the study.
Endoscopy was done as part of routine patient
management and informed consent was sought from
each study participant
Two hundred nineteen patients were enrolled into the
study. Three patients were excluded because they could
not withstand the EGD procedure.
Endoscopic diagnosis included: CAE 57 patients
(20%), oesophagitis 11 patients (4%), oesophageal-
varices 14 patients (5%), oesophageal ulcers 1 patient
(<1%), candida oesophagitis 15 patients (5%),
oesophageal stricture 7 patients (2%), cancer-stomach
11 patients (4%), gastritis 60 patients (21%), gastric
ulcers 7 patients (2%), duodenal ulcers 16 patients (%)
and duodenitis 13 patients (%). In 75 patients (26%)
there were no abnormalities.
Fifty five (19%) subjects had a histologically
proven CAE, 92.5 % of them were squamous cell
carcinomas (Table 1). The median age of those with a
CAE was 60 years in contrast to those with no CAE,
which was 45 years (p < 0.001). The majority of patients
presenting with CAE were men (69%), compared to
approximately half (49%) in non-CAE patients 49% (p
Table 1: Comparison of socio-demographic characteristics of patients with and without histologically
proven cancer of esopagus
Median age (years)
African Health Sciences Vol 8 No 2 June 2008
Epigastric pain (70% vs. 15%) and haematemesis (15% vs. 2%) were reported more frequently by patients without
CAE compared to those with CAE, (p<0.05) (Table 2). On the other hand dysphagia (80% vs. 12%) and odynophagia
(11% vs. 3%) were reported more often in patients with CAE (p<0.05).
Table 2: Symptoms in Ca-esophagus and non Ca-esophagus patients
29.750 13.270-71.890 <0.001
1.709 0.158-10.793 0.623
† A patient can have more than 1 symptom.
* Other symptoms included melena, chest pain, ascites, chocking, continous belching and diarrhea
In 49 out of 76 patients (64%) referred with a
clinical diagnosis of CAE or oesophageal stricture and
in 51 of 57 patients (89%) with an endoscopic diagnosis
of CAE, a diagnosis of CAE was confirmed histologically.
CAE were located 26% in the upper third, 40%
in the middle third and 34% in the lower third of the
oesophagus (Table 3). Squamous cell carcinoma was
found in 100% of tumours of the upper third, 91% of
tumours of the middle third, and 83% of tumours of the
lower third. Four patients had a histological diagnosis of
adenocarcinoma of the oesophagus; one patient had a
histological diagnosis of intra-epithelia metaplasia.
Table 3: Histological findings by anatomical site of the biopsy lesion
Location of tumor growth
Squamous cell 14(100%)
Site not recorded
19(91%) 15(83%) 2(100%)
More subjects with CAE smoked in contrast
to those without CAE (51% vs. 19%, p<0.001) (Table
4). Alcohol was consumed in 75% of subjects with CAE
and in 46% of subjects without CAE (p=0.001). More
CAE patients were moderate/heavy drinkers compared
to the non-CAE patients (40% vs. 23%, p= 0.010). The
use of spring/well drinking water was more often
reported by patients with CAE compared to those
without CAE (64% vs. 47%, p = 0.024), conversely
use of tap drinking water was less often reported by
patients with CAE compared to those without CAE
(24% vs. 48%, p = 0.002). HIV serology was performed
in only 37% of all of the study subjects; 19% of them
were HIV seropositive.
Mulitivariate logistic regression identified
gender, age and smoking as significant independent
predictors of CAE. Use of spring/well drinking water
or alcohol use was no significant predictor of CAE when
adjusted for age, gender and smoking habits (Table 5).
African Health Sciences Vol 8 No 2 June 2008
Table 4: Potential risk factors for cancer of the esophagus
Relative with cancer
41(75%)107(46%) 3.42(1.77, 6.61)<0.001
22(40%) 53(23%) 2.25(1.21, 4.19) 0.010
31(56%)136(59%) 0.91(0.50, 1.65)0.760
† crude odds-ratio obtained from using age (expressed in decades) as linear effect in the logistic regression model
‡ men > 2 standard drinks/day, women: >1 standard drinks/day where 1 standard drink is more than 500 mls of beer
or 100 mls of local alcohol
Table 5: Multivariate logistic regression of factors associated with cancer of the esophagus
Risk factorCrude OR
1.58 (1.31, 1.89)
2.35 (1.26, 4.41)
4.80 (2.44, 8.51)
3.42 (1.77, 6.61)
Adjusted OR P-value
1.63 (1.34, 1.98) <0.001
2.17 (1.07, 4.41) 0.032
3.63 (1.82, 7.23) <0.001
1.55 (0.71, 3.40) 0.272
Age (OR/10 years)
Any Alcohol use †
† When added to multivariate logistic regression model adjusted for age, gender, and smoking
A high percentage (19%) of patients referred for
endoscopy at Mulago hospital was found to have a CAE.
In the majority of them, the CAE was a squamous cell
carcinoma. A nearly equal number of squamous cell
carcinoma was observed in all parts of the oesophagus
but in the lower part, as expected, a few adenocarcinomas
were also detected.
In industrialized countries, a rise in
adenocarcinoma of the oesophagus, surpassing squamous
cell carcinoma, has been noticed. In Uganda the
prevalence of squamous cell CAE has remained high
compared to adenocarcinoma 19,20 Secondly, in contrast
with a male to female ratio of squamous cell carcinoma
of for example 5:1 in Ireland 21 in this study this ratio
was 2:1, as was also previously reported in other studies
from Uganda 19,20 , The reason for this difference is not
clear but could be a result of smoking habits in the two
In nearly all patients referred with a clinical
diagnosis of CAE this diagnosis was confirmed
histologically. It has to be mentioned however that certain
patients were referred for endoscopy based on the result
of barium swallow.
Smoking was associated with CAE. This is in
congruence many other studies that have identified
smoking as a risk factor for CAE, more so for squamous
cell carcinoma than for adenocarcinoma.
In our study, squamous cell carcinoma was the
most common CAE. This concurs with a retrospective
study carried out in western Kenya where also 90% of
the CAE were squamous cell carcinoma.
Many patients referred to endoscopy unit of Mulago
hospital present with CAE and squamous cell carcinoma
is the commonest histological type. Older age, male
gender and smoking were identified as risk factors in
this study. Therefore there is need to strengthen anti-
African Health Sciences Vol 8 No 2 June 2008 Download full-text
smoking campaigns also to prevent CAE. The
contribution of other potential risk factors such as
human immunodeficiency syndrome and Human
Papilloma Virus needs to be investigated.
Acknowledgements: J Menten for statistical advice
and the SIDA-SAREC grant for the funding this study
through the Faculty of Medicine. The authors do not
have a conflict of interest.
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