Elsevier

European Journal of Cancer

Volume 39, Issue 17, November 2003, Pages 2487-2494
European Journal of Cancer

Are carcinomas of the cardia oesophageal or gastric adenocarcinomas?

https://doi.org/10.1016/S0959-8049(03)00664-6Get rights and content

Abstract

There is a clear relationship between Barrett's oesophagus and oesophageal adenocarcinoma, and between Helicobacter pylori and gastric cancer, but the histogenesis of cardiac adenocarcinomas is unknown. Some clues as to possible disease associations may be provided by the pattern of gastritis. In our study, we analysed gastritis associated with oesophageal, cardiac and gastric adenocarcinomas according to the Sydney classification. Chronic gastritis was more common in gastric (88%) than in cardiac (56%) and oesophageal adenocarcinomas (38%). H. pylori was significantly more prevalent in gastric (73%) than in cardiac (34%) or oesophageal (21%) adenocarcinomas. Our results show that factors other than H. pylori must be involved in the histogenesis of cardiac adenocarcinomas. As the pattern of gastritis and the clinical features of cardiac adenocarcinomas are more comparable to oesophageal carcinomas than gastric carcinomas, we speculate that most of these tumours share similar aetiological factors with oesophageal carcinomas.

Introduction

Epidemiological studies reveal that gastric cancer is the second most common cause of cancer mortality worldwide [1]. However, during the past few decades the overall incidence rates of gastric adenocarcinomas have gradually decreased in the United States of America (USA) and Western Europe, but this decline does not apply to all forms of gastric cancer 2, 3. In contrast to the decline in the incidence of gastric cancer, the incidence rates of cardiac cancer have dramatically increased, up to 4–5% annually in the USA [4]. Simultaneously, there has been a dramatic shift in the incidence of oesophageal squamous carcinomas towards adenocarcinomas, as a result of which the latter account for 50% of the oesophageal cancers in Western Europe and USA [5]. In keeping with the parallel increase in incidence, oesophageal adenocarcinomas and cardiac adenocarcinomas share some epidemiological features, which distinguish them from adenocarcinomas of the distal part of the stomach. There is an equal gender distribution in gastric carcinomas, but the male/female ratio in oesophageal and cardiac carcinomas is 9.2 and 5.5, respectively. The disease, both in the distal oesophagus and the cardia, is most common in middle-aged patients [6]. A survival analysis has shown that patients with an adenocarcinoma of the cardia have a similar survival to those having an adenocarcinoma of the distal oesophagus [7].

The dramatic increase in incidence of oesophageal carcinomas is related to the well-established association of gastro-oesophageal reflux and Barrett's oesophagus [8]. Additional risk factors, involved in the development of oesophageal adenocarcinomas, are smoking and a poor socio-economic status. According to some authors, these risk factors are also found in association with cardiac adenocarcinomas 9, 10. Other studies could not confirm these results and showed either no relationship or an opposite relationship in which a high socio-economic status was related to cardiac cancer 11, 12. Some authors found that smoking was associated with a higher risk for the development of gastric cancer 13, 14. Thus, neither smoking nor socio-economic status could allow differentiation of risk by anatomical sub-site.

In contrast to the plethora of studies concerning the aetiopathogenesis of oesophageal adenocarcinoma, the histogenesis of cardiac adenocarcinomas is less clear. Although both adenocarcinomas share similar epidemiological characteristics, the relationship between gastro-oesophageal reflux and adenocarcinomas of the cardia is less obvious. According to some authors, ‘carditis’ is a more sensitive marker of gastro-oesophageal reflux that could even precede the clinical signs of refluxoesophagitis. Others, however, could not confirm this 15, 16, 17. They believe that inflammation of the cardia is part of a Helicobacter pylori-related pangastritis. However, the role of H. pylori in the development of cardiac adenocarcinomas is uncertain. For example, the rising incidence of cardiac cancers is in contrast to the decline of H. pylori infection in the same populations. The relationship between H. pylori chronic pangastritis and gastric cancer is more firmly established, as the infection is associated with a 9-fold increased risk for this type of cancer [18]. As would be expected, the decrease in H. pylori infection is paralleled by a decline in the prevalence of gastric cancer [19].

Hence, the purpose of this study was to analyse the inflammatory changes present in the gastric mucosa in cases of oesophageal and cardiac adenocarcinomas, according to the updated Sydney system [20]. The same assessment has been performed on gastric biopsies of a control population with gastric carcinomas. Special attention has been given to the presence of H. pylori in the inflamed mucosa.

Section snippets

Patients and methods

Our retrospective study comprised 342 patients, who underwent surgery for an adenocarcinoma of the oesophagus or stomach between 1993 and 2000 at the University Hospitals in Leuven, Belgium. The tumours were classified as oesophageal, cardiac or gastric cancer on the basis of two parameters: (1) the localisation of the major bulk of the tumour, and/or (2) the presence or absence of Barrett's oesophagus, determined on preoperative endoscopic biopsies or using tissue from the resection specimen,

Classification of the proximal tumours (Table 1)

The 342 tumours in our study population were classified according to the different criteria.

When we categorised our 242 proximal tumours according to the localisation of the bulk of the tumoral mass, 98 (40%) and 94 (39%) tumours were lower oesophageal and cardiac adenocarcinomas, respectively. 50 patients had a tumour centred on the gastro-oesophageal junction, and these tumours were classified as gastro-oesophageal junction-adenocarcinomas (21%).

A Barrett's oesophagus, as defined above, was

Discussion

It is commonly accepted that H. pylori is a risk factor for the development of gastric cancer. The histogenesis of this type of cancer is a multifactorial process involving a progressive evolution from superficial gastritis, atrophy, intestinal metaplasia, dysplasia to cancer [25]. Although other aetiopathogenetic factors are likely to be involved in this process, infection with H. pylori is associated with a 9-fold increased risk for gastric cancer 18, 25. Similar to gastric cancer, the

Acknowledgments

We gratefully acknowledge Prof. Dr. M. Dixon for his help in the preparation of this manuscript.

References (58)

  • J.R Goldblum et al.

    Inflammation and intestinal metaplasia of the gastric cardiathe role of gastroesophageal reflux and H. pylori infection

    Gastroenterology

    (1998)
  • G.W.B Clark et al.

    Nodal metastasis and sites of recurrence after en bloc esophagectomy for adenocarcinoma

    Ann. Thorac. Surg.

    (1994)
  • F.H Ellis et al.

    Esophagogastrectomy for carcinoma of the esophagus and cardiaa comparison of findings and results after standard resection in three consecutive eight-year intervals with improved staging criteria

    J. Thorac. Cardiovasc. Surg.

    (1997)
  • D.M Parkin et al.

    Estimates of the worldwide incidence of eighteen major cancers in 1985

    Int. J. Cancer

    (1993)
  • S Hansen et al.

    Esophageal and gastric carcinoma in Norway 1958–1992incidence time trend variability according to morphological subtypes and organ subsites

    Int. J. Cancer

    (1997)
  • C.P Howson et al.

    The decline in gastric cancerepidemiology of an unplanned triumph

    Epidemiol. Rev.

    (1986)
  • W.J Blot et al.

    Rising incidence of adenocarcinoma of the esophagus and the gastric cardia

    JAMA

    (1991)
  • T.R DeMeester

    Esophageal carcinomacurrent controversies

    Semin. Surg. Oncol.

    (1997)
  • G.W.B Clark et al.

    Is Barrett's metaplasia the source of adenocarcinomas of the cardia?

    Arch. Surg.

    (1994)
  • K Dolan et al.

    New classification of oesophageal and gastric carcinomas derived from changing patterns in epidemiology

    Br. J. Cancer

    (1999)
  • J Lagergren et al.

    Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma

    N. Engl. J. Med.

    (1999)
  • L.M Brown et al.

    Adenocarcinoma of the esophagus and esophagogastric junction in white men in the United Statesalcohol, tobacco, and socioeconomic factors

    Cancer Causes Control

    (1994)
  • J Lagergren et al.

    The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia

    Int. J. Cancer

    (2000)
  • M.D Gammon et al.

    Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia

    J. Natl. Cancer Inst.

    (1997)
  • J Powell et al.

    Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites

    Br. J. Cancer

    (1990)
  • W Ye et al.

    Tobacco, alcohol and the risk of gastric cancer by sub-site and histologic type

    Int. J. Cancer

    (1999)
  • Z.-F Zhang et al.

    Adenocarcinomas of the esophagus and gastric cardiamedical conditions, tobacco, alcohol and socioeconomic factors

    Cancer Epidemiol. Biomarkers Prev.

    (1996)
  • D.J Bowrey et al.

    Inflammation at the cardio-oesophageal junctionrelationship to acid and bile exposure

    Eur. J. Gastroenterol. Hepatol.

    (2003)
  • S Oberg et al.

    Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease

    Ann. Surg.

    (1997)
  • Cited by (22)

    • Correlation between genomic alterations assessed by array comparative genomic hybridization, prognostically informative histologic subtype, stage, and patient survival in gastric cancer

      2011, Human Pathology
      Citation Excerpt :

      In fact, 8p23.1 deletions have recently been shown to have a role in the genesis of diaphragmatic hernia [27], a known cause of gastroesophageal reflux disease, which in turn is known to be related with esophageal and cardial adenocarcinoma [28]. Indeed, adenocarcinoma of the cardia and gastroesophageal junction differs in several aspects from more common distal gastric cancer, for instance, concerning the role of Helicobacter pylori or EBV infection and epidemiology [29]. Thus, a distinctive role of pertinent genetic lesions would not be surprising.

    • Prognostic factors for patients with gastric cancer after surgical resection

      2006, Reports of Practical Oncology and Radiotherapy
    • Surgical treatment of tumors of the proximal stomach with involvement of the distal esophagus: A 26-year experience with Siewert type III tumors

      2006, Journal of Thoracic and Cardiovascular Surgery
      Citation Excerpt :

      The placement of a downstream feeding jejunostomy tube at the time of the initial operation is also helpful in managing these complications, if they occur. Although AEG tumors have recently been acknowledged as a unique clinical entity, few studies have examined type III tumors as a distinct group; instead, most studies group all 3 types together.6,15,16 This might be inappropriate, however, because type III tumors appear to have a poorer long-term survival, with overall 5-year survival of approximately 20% to 25%.8,9,17

    View all citing articles on Scopus
    1

    Current address: Department of Hepatogastroenterology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium.

    View full text