a Queen Elizabeth Hospital, University of Birmingham, UK. E-mail: Janusz.Jankowski{at}university-b.wmids.nhs.uk
b Department of Maxillofacial Surgery, University of Bristol, Bristol, UK.
The incidence of oesophageal adenocarcinoma (OA) has seen a rapid increase throughout the last 20 years in the western world and has now surpassed that of oesophageal squamous carcinomas in developed countries. The diagnosis is often at an advanced stage and is almost uniformly associated with a poor prognosis and mean survival of less than one year.1 Oesophageal adenocarcinoma is strongly associated with gastro-oesophageal reflux disease (GORD) and Barrett's Metaplasia (BM). It is now widely accepted that OA does not develop de novo but rather along a sequence of phenotypic and genetic alterations that have been termed the metaplasia-dysplasia-neoplasia sequence.2
Much attention has been devoted in this context to BM and subsequently the potential to curtail the increase in OA by surveillance programmes for patients with BM. Surveillance programmes were initially widely advocated but unfortunately so far have failed to impact on the rising incidence of OA and some studies have questioned their cost-effectiveness.3 At least some of these failures have been attributed to problems related to sampling errors and inaccuracies in the diagnosis of BM due to the lack of accurate landmarks at the gastro-oesophageal junction. Another reason has been a lack of accurate figures regarding the incidence of OA, the incidence of BM and the annual conversion rates from BM to OA.
Gastro-oesophageal reflux is very common in the western world with up to 30% of the population expected to suffer symptoms per month.4 Barrett's metaplasia is often asymptomatic and only develops in the minority of patients with an estimated incidence of 0.5% in the US and possibly twice that in the UK. Conversion rates for BM to dysplasia and OA are generally low and are thought to be around 0.22% annually (Table 1). Regional variations in the western world have also become apparent with an annual incidence of OA of 35/ 100 000 in the US compared with 1216/100 000 in the UK.5,6 Some of these figures have, however, recently been questioned as higher than expected due to a possible reporting bias, but they tend uniformly to suggest regional differences.7 The success of surveillance programmes and the provision of cancer resources depend heavily on these facts and highlight's the importance of the paper by Corley and Buffler8 in this issue of the International Journal of Epidemiology.
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Similarities between adenocarcinoma of the oesophagus and the nearby, but distinct gastric cardia have led epidemiologists to present adenocarcinoma at these sites as the same disease. Corley and Buffler highlight the need to precisely discriminate between the sites. Differences in their pathogenesis have emerged in recent years with strong associations between GORD with OA and Helicobacter pylori infection with gastric cardia adenocarcinomas (GCA). These differences are to an extent confirmed by the discordance of incidences in the populations studied. Gastric cardia adenocarcinomas, as well as H. pylori infection are particularly common in populations of Chinese and Malaysian ethnicity and suggest a possible genetic predisposition. Host responses to H. pylori infection and in particular polymorphisms of cytokines such as Interleukin 1ß are increasingly recognized as being important in gastric carcinogenesis.9 Obesity also varies in its association with adenocarcinomas at the gastro-oesophageal junction. It is strongly associated with OA and less so with GCA and in one study this finding was independent of GORD.4 The mechanism for the link with body fat and the role other putative risk factors needs to be clarified.
Possibly the greatest importance of the paper by Corley and Buffler lies in identifying groups most at risk of OA or GCA and hence most likely to benefit from interventional strategies such as surveillance endoscopies or H. pylori eradication. Acid suppression for BM by long-term treatment with proton pump inhibitors (PPI) have been the mainstay of treatment with encouraging reports of partial regression of areas of BM.10 There are, however, no long-term outcome data and hence closer follow-up of populations at high risk such as Scotland might yield answers in a cost effective manner.
The benefits are not only restricted to favourable clinical outcomes and cost effectiveness, but have huge implications for basic research and drug development. Our knowledge about the molecular mechanisms involved in the BM-dysplasia-neoplasia sequence of OA has identified several targets, ranging from cytokines such as tumour necrosis factor (TNF
) to enzymes involved with oncogene activation such as tyrosine kinases and cyclo-oxygenase 2 (COX-2), for pharmaceutical intervention and potential chemoprevention.11 Targeting of at-risk populations will be crucial in the design of future experimental pharmaceutical trials and establishes the UK as likely candidate.
References
1
Jankowski JA, Perry I, Harrison RF. Gastro-oesophageal cancer: death at the junction. Br Med J 2000;321:46364.
2
Jankowski JA, Wright NA, Meltzer SJ et al. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 1999;154:96573.
3
Macdonald CE, Wicks AC, Playford RJ. Final results from 10 year cohort of patients undergoing surveillance for Barrett's oesophagus: observational study. Br Med J 2000;321:125255.
4
Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:82531.
5 Jankowski J. CRC CancerStats: Oesophageal Cancer. London, UK: Cancer Research Campaign Press, 2001.
6 Devesa SS, Blot WJ, Fraumeni JF. Changing patterns in the incidence of oesophageal and gastric cancer in the United States. Cancer 1998; 83:204953.[ISI][Medline]
7 Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS. Is there publication bias in the reporting of cancer risk in Barrett's Oesophagus? Gastroenterology 2000;119:33338.[ISI][Medline]
8
Corley DA, Buffler PA. Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database. Int J Epidemiol 2001;30:141525.
9 El Omar EM, Carrington M, Chow WH et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000;404:398402.[ISI][Medline]
10
Triadafilopoulos G. Proton pump inhibitors for Barrett's oesophagus. Gut 2000;46:14446.
11 Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G. Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology 2000;118:48796.[ISI][Medline]
12 Cooper BT, Barbezat GO. Barrett's oesophagus: a clinical study of 52 patients. Q J Med 1987;62:97108.[Medline]
13 Robertson CS, Mayberry JF, Nicholson DA, James PD, Atkinson M. Value of endoscopic surveillance in the detection of neoplastic change in Barrett's oesophagus. Br J Surg 1988;75:76063.[ISI][Medline]
14 Watson RG, Porter KG, Sloan JM. Incidence of adenocarcinoma in Barrett's esophagus and an evaluation of endoscopic surveillance. Eur J Gastroenterol Hepatol 1991;3:15962.[ISI]
15 Iftikhar SY, James PD, Steele RJ, Hardcastle JD, Atkinson M. Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma. Gut 1992;33:115558.[Abstract]
16 Moghissi K, Sharpe DA, Pender D. Adenocarcinoma and Barrett's oesophagus. A clinico-pathological study. Eur J Cardiothorac Surg 1993; 7:12631.[Abstract]
17 Wright TA, Gray MR, Morris AI et al. Cost effectiveness of detecting Barrett's cancer. Gut 1996;39:57479.[Abstract]
18 Rana PS, Johnston DA. Incidence of adenocarcinoma and mortality in patients with Barrett's oesophagus diagnosed between 1976 and 1986: implications for endoscopic surveillance. Dis Esophagus 2000;13:2831.[ISI][Medline]
19 Bani-Hani K, Sue-Ling H, Johnston D, Axon AT, Martin IG. Barrett's oesophagus: results from a 13-year surveillance programme. Eur J Gastroenterol Hepatol 2000;12:64954.[ISI][Medline]
20
Macdonald CE, Wicks AC, Playford RJ. Final results from 10 year cohort of patients undergoing surveillance for Barrett's oesophagus: observational study. Br Med J 2000;321:125255.
21 Spechler SJ, Robbins AH, Rubins HB et al. Adenocarcinoma and Barrett's esophagus. An overrated risk? Gastroenterology 1984;87:92733.[ISI][Medline]
22 Cameron AJ, Ott BJ, Payne WS. The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. N Engl J Med 1985;313:85759.[Abstract]
23 Achkar E, Carey W. The cost of surveillance for adenocarcinoma complicating Barrett's esophagus. Am J Gastroenterol 1988;83:29194.[ISI][Medline]
24 Williamson WA, Ellis FH, Jr, Gibb SP et al. Barrett's esophagus. Prevalence and incidence of adenocarcinoma. Arch Intern Med 1991; 151:221216.[Abstract]
25 Reid BJ, Blount PL, Rubin CE, Levine DS, Haggitt RC, Rabinovitch PS. Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort. Gastroenterology 1992;102:121219.[ISI][Medline]
26
McDonald ML, Trastek VF, Allen MS, Deschamps C, Pairolero PC, Pairolero PC. Barretts's esophagus: does an antireflux procedure reduce the need for endoscopic surveillance? J Thorac Cardiovasc Surg 1996; 111:113538.
27 Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 1997;92:21215.[ISI][Medline]
28 Weston AP, Krmpotich PT, Cherian R, Dixon A, Topalosvki M. Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus. Am J Gastroenterol 1997;92:40713.[ISI][Medline]
29 Streitz JM, Jr, Ellis FH, Jr, Tilden RL, Erickson RV. Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer. Am J Gastroenterol 1998;93:91115.[ISI][Medline]
30 Katz D, Rothstein R, Schned A, Dunn J, Seaver K, Antonioli D. The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett's esophagus. Am J Gastroenterol 1998;93: 53641.[ISI][Medline]