Shanmugarajah Rajendra

Ethnic differences in the prevalence of endoscopic esophagitis and Barrett's esophagus: The long and short of it all

Recent studies indicate that the prevalence of gastroesophageal reflux disease in Asia is either increasing or better recognized. There is a paucity of reliable data on the prevalence of reflux disease in the various races in general and in Malaysia, in particular. The prevalence of erosive esophagitis and Barretts esophagus in a multiethnic Malaysian population was studied, as well as the relationship of various factors associated with reflux disease. Chinese, Malay, and Indian patients undergoing gastroscopy in a tertiary referral center were assessed for the presence of esophagitis, hiatus hernia, and Barretts esophagus. Patient demographics and risk factors associated with gastroesophageal reflux disease were also documented. The prevalence of endoscopically documented esophagitis among 1985 patients was 6.1%, the majority of which were mild, Grade I or II (88%). There was a preponderance of Indians with esophagitis, as well as males (P<0.05) and those with the presence of a hiatus hernia (P<0.01). Long-segment Barretts esophagus was found in 1.6% of patients, and short-segment Barretts in 4.6%. Indians had the highest prevalence of Barretts esophagus compared with Chinese (P<0.05) or Malays (P<0.01). Hiatus hernia and erosive esophagitis were both positively associated with Barretts metaplasia (P<0.01). A significant proportion of Malaysian patients undergoing endoscopy has mild reflux esophagitis and Barretts esophagus. Indian ethnicity and the presence of a hiatus hernia were significantly associated with endoscopic esophagitis and Barretts metaplasia. These observed racial differences warrant further study.

Helicobacter pylori, ethnicity, and the gastroesophageal reflux disease spectrum: a study from the East.

Background:  Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored.

Prevalence of irritable bowel syndrome in a multi-ethnic Asian population

Sirs, In relation to the recent article by Lu et al. on the prevalence, social impact and health-seeking behaviour of irritable bowel syndrome patients in Taiwan, we would like to share our own prevalence data on irritable bowel syndrome in a multi-racial Asian population. It is widely believed that irritable bowel syndrome is rather uncommon in Asia. Prevalence studies on irritable bowel syndrome in Asia have reported varying results: Singapore (2.3%), Thailand (4.4%), Hong Kong (6.6%, Rome II criteria), China (22.8%, Manning criteria), Bangladesh (24.4%, Manning criteria; 8.5%, Rome I criteria) and Taiwan (22.1%, Rome II criteria). This may be due to the use of questionnaires based on different definitions of functional gastrointestinal disorders and to variations in the study populations and sampling methods. Differences in socio-economic status and cultural practices and the rapidly changing lifestyle of the affluent East Asian population may also be responsible for the disparity in the reported prevalence rates of irritable bowel syndrome. Racial differences within different communities in the same country (if any) have remained largely unexplored. Malaysia affords a suitable population base to study such differences in the prevalence of irritable bowel syndrome. We therefore undertook to estimate the prevalence of irritable bowel syndrome using a locally validated Rome II Modular Questionnaire. Additional questions pertaining to heartburn, acid regurgitation, physician visits and treatment (Western or alternative medicine) were also included. The study population was from the State of Perak (population approximately 2 million) whose ethnic composition is as follows: Malays, 51.4%; Chinese, 31.3%; Indians, 12.8%; others, 4.5%. This ethnic distribution and basic demographic characteristics are representative of the rest of west Malaysia. Subjects were identified from the National Household Sampling Frame created for the 2000 Population and Housing Census. Subjects were recruited from both rural and urban areas using a race-stratified disproportionate random sampling procedure to ensure a sufficient number of members of ethnic minorities. To avoid ethnic ambiguity, only those subjects without racial admixture in the immediate two preceding generations were recruited. A team of interviewers trained by one physician (SR) interviewed the subjects at home in the languages⁄dialect usually understood and spoken by the respondents. A total of 1179 selected individuals were interviewed, but questionnaires returned by 949 subjects only (314 Malays, 314 Chinese, 321 Indians) were successfully analysed. They were aged between 18 and 81 years (mean, 33.6 years; s.d., 13 years); 478 were males and 471 were females. Irritable bowel syndrome was diagnosed in 148 individuals (39 Malays, 55 Chinese, 54 Indians; P 1⁄4 0.16), with a female to male ratio of 1.4. (irritable bowel syndrome subjects vs. controls: odds ratio, 0.65; 95% confidence interval, 0.45–0.94; P 1⁄4 0.01). Ethnic-adjusted irritable bowel syndrome prevalence rates were as follows: Malays, 12.4%; Chinese, 17.5%; Indians, 16.8%. The race-standardized prevalence of irritable bowel syndrome was 14% with no significant ethnic differences (P 1⁄4 0.08). Eightythree patients with irritable bowel syndrome (56%) reported heartburn at least once a year, compared with 236 in the control group (29%) (irritable bowel syndrome subjects vs. controls: odds ratio, 3.06; 95% confidence interval, 2.10–4.4; P < 0.001). There were no significant differences in higher educational attainment or socio-economic class between subjects with irritable bowel syndrome and controls. Constipationpredominant irritable bowel syndrome was recorded in 36.5%, diarrhoea-predominant in 35.1% and mixed pattern in 28.4%. Amongst those with irritable bowel syndrome, 64 (43.2%) had consulted a doctor and 74 (50%) had taken medication (Western and alternative). Our data confirmed the reported association between gastro-oesophageal reflux and irritable bowel synAliment Pharmacol Ther 2004; 19: 707–708. doi: 10.1111/j.1365-2036.2004.01891.x

Transcriptionally Active Human Papillomavirus Is Strongly Associated With Barrett's Dysplasia and Esophageal Adenocarcinoma

OBJECTIVES:The role of human papillomavirus (HPV) in Barretts esophagus (BE) remains unclear. The few studies that have previously investigated HPV and esophageal adenocarcinoma (EAC) or BE have produced either negative data or positive results of doubtful clinical/etiological significance or have detected only low-risk HPV types. We therefore prospectively determined the prevalence of biologically active HPV in esophageal epithelium of patients representing the Barretts metaplasia–dysplasia–adenocarcinoma sequence.METHODS:HPV DNA was estimated by nested PCR and viral transcriptional activity detected by E6/7 oncogene mRNA expression and p16INK4A immunohistochemistry in fresh frozen and paraffin-embedded esophageal biopsies of patients with BE, Barretts dysplasia (BD), and EAC, as well as controls. Biopsies were obtained from the transformation zone (squamocolumnar junction (SCJ)) and the lesion, or corresponding site in controls, i.e., 2 cm above the gastroesophageal junction (GEJ).RESULTS:Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78–4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69–4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60–1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86–59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87–59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01–15.3, P=0.048) respectively). In 66 HPV DNA–positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3–529, P<0.001; lesion: OR 62.2, 95% CI 12.4–311, P<0.001) than when all were negative.CONCLUSIONS:Transcriptionally active HR-HPV was strongly associated with BD and EAC, but was largely biologically irrelevant in BE and controls, suggesting a potential role in esophageal carcinogenesis. These data provide robust justification for further detailed longitudinal, interventional, and molecular studies.

Racial differences in the prevalence of heartburn

Sirs, We read with interest the article by Wong et al. on the prevalence of gastro-oesophageal reflux disease (GERD) in a Chinese population and that by Spechler et al. on racial differences in GERD. We would like to share our own data on racial disparity in the prevalence of heartburn in an ethnically mixed non-migrant Asian population. The prevalence of GERD amongst Asians has been reported to be low and has been attributed to a lack of a word for heartburn in the Chinese language, the smaller body mass of Asians, the low-fat Asian diet and the high prevalence of Helicobacter pylori infection. Indeed, there is no word for heartburn in certain other languages spoken in Asia, e.g. Tamil and Malay. Not surprisingly, Spechler et al. found significant differences amongst racial groups in the reporting, understanding and experience of heartburn, which were exceedingly low in East Asians (2.6%) when compared with Caucasians (34.6%) and Afro-Americans (46.1%). Studies from Taiwan report prevalence rates for erosive oesophagitis and Barrett’s oesophagus of 15% and 2%, respectively, both of which approach those of published Western reports. 6 Our own data from Malaysia reveal a prevalence rate of endoscopically documented oesophagitis of 6% and a similar value for biopsyproven Barrett’s oesophagus (both long and short segments), i.e. not dissimilar to published Western data. In view of the conflicting prevalence data on GERD in different geographical locations within Asia and the ethnic differentiation in the prevalence of oesophagitis and Barrett’s metaplasia, we studied the prevalence of heartburn and health care-seeking behaviour in a multi-racial population. Furthermore, we sought to determine the proportion seeking treatment for GERD, be it Western or alternative medicine. In our cross-sectional study, we used the Gastrointestinal Symptoms Questionnaire previously validated in an Asian (Singaporean) population with a similar multi-racial mix, provided by Ho et al. Our questionnaire contained 24 ⁄121 response items in relation to GERD in the last year. Heartburn was defined as a burning feeling rising from the stomach or lower chest up towards the neck, and acid regurgitation as a very sour or acid-tasting fluid at the back of the throat. In particular, the severity and duration of heartburn, nocturnal awakening and aggravating and relieving factors were all included in the questionnaire, as were frequent psychosomatic symptoms. The study population was from the State of Perak (population, approximately 2 million) whose ethnic composition is as follows: Malays, 51.4%; Chinese, 31.3%; Indians, 12.8%; others, 4.5%. This ethnic distribution and basic demographic characteristics are representative of the rest of west Malaysia. Subjects were identified from the National Household Sampling Frame created for the 2000 Population and Housing Census. Subjects were recruited from both rural and urban areas using a race-stratified disproportionate random sampling procedure to ensure a sufficient number of members of ethnic minorities. To avoid ethnic ambiguity, only subjects without racial admixture in the immediate two preceding generations were recruited. A team of interviewers trained by one physician (SR) interviewed the subjects at home in the languages ⁄ dialect usually understood and spoken by the respondents. Subjects aged 18–81 years (mean, 33.6 years; standard deviation, 13 years), who were successfully interviewed and analysed, totalled 949 (478 males, 471 females), consisting of 314 Chinese, 314 Malays and 321 Indians. Heartburn at least once a year was reported by 319 (33.6%) respondents, with a female to male ratio of 1.3. Monthly and weekly prevalence rates were 31 (9.7%) and 19 (6.0%), respectively. The prevalence of annual heartburn by ethnic group was as follows: Chinese, 92 (29.3%); Malays, 91 (29%); Indians, 136 (42.4%) (Indians vs. Chinese: odds ratio, 1.77; 95% confidence interval, 1.26–2.50; P < 0.001; Indians vs. Malays: odds ratio, 1.80; 95% confidence Aliment Pharmacol Ther 2004; 19: 375–378. doi: 10.1111/j.1365-2036.2004.01814.x

Colonic diverticular disease in a multiracial Asian patient population has an ethnic predilection.

Background Traditionally, diverticular disease of the colon has been attributed to ageing, low dietary fibre and a high intraluminal pressure. Recently, genetic and racial factors have also been implicated. Methods Four-hundred and ten consecutive multiracial Asian patients undergoing colonoscopy for a variety of bowel symptoms in a private endoscopy unit were studied for differing frequencies (if any) in colonic diverticular disease and concomitant abnormalities. Results Forty-one patients (10%) had diverticular disease. Diverticula were present in 22/147 Chinese (15%), 14/153 Indians (9%) and 5/110 Malays (4.5%). The mean age of patients with diverticular disease was 55 years as compared with 51.3 years in those without (P=0.12) and there was no gender difference. Thirty-six patients (88%) had diverticula in the right colon only, four patients (10%) exclusively in the left hemicolon, and one patient (2%) had bilateral involvement. Using regression analysis, Chinese ethnicity [odds ratio (OR)=2.11; 95% confidence interval (CI), 1.09–4.09; P=0.027), constipation (OR=2.65; 95% CI, 1.23–5.42; P=0.007) and colorectal adenomas (OR=2.65; 95% CI, 1.08–6.46; P=0.033) were independently associated with diverticular disease. Conclusions Colonic diverticular disease in a multiracial Asian patient population has an ethnic predilection and is predominantly right-sided.

Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians – a preliminary study

Background : Characteristic immune profiles have been demonstrated in gastro‐oesophageal reflux disease. However, the genetic basis of gastro‐oesophageal reflux disease remains unclear.

Infection and esophageal cancer

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on infection and cancer, and includes commentaries on the influence of bacterial infections on mucin expression and cancer risk; the role of esophageal bacterial biota in the incidence of esophageal disease; the association between human papilloma virus (HPV) and esophageal squamous cell carcinoma; the role of HPV in esophageal adenocarcinoma; the role of Helicobacter pylori in cardiac carcinoma; and the role of Epstein–Barr virus infection in esophageal cancer.

The Effect of H2 Antagonists on Proliferation and Apoptosis in Human Colorectal Cancer Cell Lines

Cimetidine is known to enhance the survival of gastro-intestinal cancer patients, though the mechanisms involved are incompletely understood. Postulated modes of action include blocking the proliferative effect of tumors and inhibiting T suppressor cell activity, both of which are thought to be mediated by histamine type 2 receptors. Apoptotic cell death may offer an alternative explanation for reduced cell growth. We aimed to examine the effects of histamine, cimetidine, and ranitidine on in vitro proliferation and apoptosis in two human colorectal cancer cell lines, Caco-2 and LoVo. A cell proliferation assay was used as an index of cell growth. Histamine receptor status was determined by quantifying cyclic adenosine monophosphate and apoptosis via DNA fragmentation. Results show that histamine (10−5 to 10−9M) had no effect on the growth of either cell line. The proliferation of Caco-2 was inhibited by ranitidine (10− 7M) alone and in combination with histamine. Cimetidine (10− 5M) only suppressed the growth of Caco-2 in the presence of histamine. The H2 antagonists had no effect on LoVo irrespective of histamine. There was no accumulation of cyclic adenosine monophosphate in Caco-2 cells in response to histamine at a similar concentration. Apoptosis was induced in Caco-2 by both antisecretory drugs, and only ranitidine caused apoptotic cell death in LoVo cells. We conclude that cimetidine and ranitidine inhibit Caco-2 cancer cells in vitro, independently of the H2 receptor. In addition, both drugs induce apoptosis in the same cell line. Growth inhibition and apoptosis are likely to contribute to the tumor regressive properties of cimetidine and ranitidine in vivo.

Similar immunogenetics of Barrett’s oesophagus and cervical neoplasia: is HPV the common denominator?

There are a number of similarities between cervical cancer and oesophageal adenocarcinoma. As cervical cancer is overwhelmingly associated with oncogenic human papillomavirus (HPV) infection, the possibility that HPV is also associated with the aetiology of oesophageal adenocarcinoma needs to be examined. This paper presents the evidence for such an association and a discussion of what further studies would be needed to confirm such an association. HPV has been identified as the major aetiological factor in cervical carcinogenesis,1 being detected in 90–100% of cervical cancer specimens compared with 20% of controls.2 In addition, the HPV viral genome has been identified in most of the precursor lesions of cervical intraepithelial neoplasia.3 HPVs are epitheliotropic and were thought to preferentially infect squamous epithelia only. However, it is now known that much of the virus is present at the squamo–columnar junction. Moreover, a consistent, strong and robust association between infection by high-risk HPV types and risk of development of adenocarcinoma of the cervix has been demonstrated.4 5 The role of HPV-mediated tumorigenesis in cervical cancer raises the question of the possible pathogenic role of the virus in oesophageal squamous and adenocarcinoma, oropharyngeal cancers and other non-genital malignancies. The recent demonstration of an association between HPV infection and oropharyngeal cancers, and the demonstration that this association may be related to direct or indirect orogenital transmission, reveals the exposure of the upper gastrointestinal tract to HPV infection.6 There is some evidence for a plausible role for HPV in the pathogenesis of squamous cell carcinoma of the oesophagus.7 High-risk-type HPV infections (predominantly HPV16 and HPV18) are detected in about 15% and 23% of patients with oesophageal squamous carcinoma using PCR and in situ hybridisation techniques, respectively.7 HPV detection rates in oesophageal cancer are highly variable in different geographical areas of …