Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Diagnosis

How to define cardiac mucosa? Can it be found in patients without gastroesophageal reflux disease? Can it be considered as a pre-Barrett change?

P. Chandrasoma (Los Angeles)

Definition of cardiac mucosa

Cardiac mucosa is a mucosa with a surface columnar epithelium that contains glands that are composed of mucous cells only. Cardiac mucosa has also been termed junctional mucosa by Hayward [1] and Paull et al. [2]. Cardiac mucosa is found only in the distal tubal esophagus and the proximal part of the gastric pouch that is called the gastric cardia. With dilatation of the distal intra-abdominal esophagus caused by shortening of the lower esophageal sphincter (LES) in patients with reflux, it is possible that the proximal part of the pouch is actually dilated esophagus ("gastricized esophagus") rather than proximal stomach. If one accepts that the gastroesophageal junction (GEJ) is defined by the proximal limit of oxyntic mucosa, proposed in the answer to my previous question, then cardiac mucosa in the proximal part of the pouch must represent esophagus rather than stomach.

While there is no controversy as to the definition of cardiac mucosa, much confusion surrounds the term "cardia". The term cardia is used in two different contexts. First, it is used synonymously with the LES (as in "achalasia of the cardia"). Secondly, it is used anatomically to define that part of the proximal stomach ("gastric cardia") that is immediately adjacent to the opening of the tubal eosphagus. The fact that the lower esophagus can become dilated makes this definition of gastric cardia questionable. In fact, when one considers the evidence that adenocarcinoma of the "proximal stomach" or "gastric cardia" is epidemiologically associated with reflux [3], there is reason to believe that what is called the proximal stomach in patients with reflux in reality represents massively gastricized esophagus. The mucosal lining of the "gastric cardia" is highly variable, and only infrequently consists of cardiac mucosa in endoscopically normal patients [4].

"Carditis" is another controversial term. To have a constant meaning, carditis must be defined as an inflammation of histologically defined cardiac mucosa, irrespective of location. When defined in this manner, carditis is etiologically related to reflux in a highly significant manner [5, 6].

Can cardiac mucosa be found in patients without gastroesophageal reflux disease and can cardiac mucosa be considered a pre-Barrett change?

Before answering this question, it is important to recognize that there is no universally accepted definition of gastroesophageal reflux disease (GERD). In the literature, GERD is defined variably by the presence of symptoms (although it is known that GERD can be asymptomatic), the presence of endoscopic and histologic changes in the squamous epithelium (although it is known that these are often absent), and the presence of an abnormal 24-hour pH study (although the sensitivity of this test is not 100%). Ambulatory 24-hour pH studies show that acid exposure of the lower esophagus is an almost universal occurrence in humans [7]. GERD cannot therefore be defined by the presence of reflux.

Any disease definition must have an end-point. Because the main threat to life in patients with reflux is adenocarcinoma, it is recommended that any definition of GERD that is developed should have adenocarcinoma as its end-point. The earliest morphologic criterion that is accepted as being associated with adenocarcinoma at the present time is Barrett's esophagus. Though Barrett's esophagus has a 100% specificity for GERD, its sensitivity is low because most patients with significant reflux do not have Barrett's esophagus; therefore it has limited value as a defining criterion for GERD.

Recent data indicate that the majority of the population do not have cardiac mucosa at the GEJ. In our study, cardiac mucosa was present only in 56% of patients even after the entire squamocolumnar junction was examined histologically at autopsy [8]. Jain et al. [4] reported that 65% of endoscopically normal patients lacked cardiac mucosa when the GEJ was extensively sampled by multiple biopsies.

Oberg et al.'s study [6] of 334 endoscopically normal patients showed that cardiac mucosa and oxynto-cardiac mucosa were absent in 88 (26%) patients. The 246 patients who had cardiac mucosa or oxynto-cardiac mucosa had significantly higher acid exposure in the 24-hour pH study than the 88 patients who had neither cardiac mucosa nor oxynto-cardiac mucosa. This suggests that cardiac mucosa and oxynto-cardiac mucosa are abnormal mucosae at the junction that result from the effect of acid on the squamous epithelium of the esophagus.

In 1976, Paull et al. [2] reported that intestinal metaplasia occurs in a mucosa that contains mucous glands only. We have also observed that goblet cells, which indicate intestinal metaplasia, do not coexist with parietal cells in the same gland. Goblet cells occur in cardiac mucosa, but almost never in oxynto-cardiac mucosa. While cardiac mucosa and oxynto-cardiac mucosa are both abnormal mucosae caused by reflux, only cardiac mucosa is complicated by intestinal metaplasia. The presence of parietal cells in glands appears to preclude the development of intestinal metaplasia. This permits the division of patients with cardiac mucosa or oxynto-cardiac mucosa into the following two groups:
- patients with cardiac mucosa, with or without oxynto-cardiac mucosa. These patients have a mucosa that has the potential to develop intestinal metaplasia (Barrett's esophagus). Intestinal metaplasia does not occur in any other mucosal type in this region. Cardiac mucosa is therefore the first recognizable morphologic change in the refluxadenocarcinoma sequence with Barrett's esophagus and dysplasia being intermediate steps (Figure 1);
- patients with oxynto-cardiac mucosa only. These patients, while showing evidence of reflux-induced mucosal abnormality, have no risk of intestinal metaplasia. They are therefore outside the reflux-adenocarcinoma sequence (Figure 1).

Taking the above data, it is recommended that the presence of cardiac mucosa in a biopsy from the junctional region be used as a histologic definition of GERD. According to this definition, patients without cardiac mucosa in a representative biopsy do not have GERD irrespective of any other criterion, and those who have cardiac mucosa have GERD. The use of a morphologic criterion is superior to criteria such as symptoms or amount of acid exposure in a 24-hour pH study because it assesses the actual effect of acid exposure on the mucosa.

If the presence of cardiac mucosa in a biopsy is accepted as the defining criterion of GERD, it will have a 100% sensitivity and 100% specificity using adenocarcinoma as the end-point for the definition. All patients with cardiac mucosa have reflux-induced epithelial damage that indicate a future risk of developing intestinal metaplasia and adenocarcinoma.

Using the presence of cardiac mucosa to define GERD has one very important practical advantage. For the first time, it provides a means of identifying the population not at risk for intestinal metaplasia and adenocarcinoma. Irrespective of symptoms or 24-hour pH

Figure 1. Epithelial transformations in the lower esophagus in reflux disease. The refluxadenocarcinoma sequence is highlighted.

study results, a patient who has no cardiac mucosa at the GEJ after adequate sampling can be confidently declared not to be at risk. A majority of the population - 56-65% in the two studies cited [4, 10] - do not have cardiac mucosa and are not at risk for intestinal metaplasia and adenocarcinoma at the time of the biopsy, assuming adequate sampling. The effect of decreasing the size of the population at risk so substantially makes it much easier to develop cost-effective prevention protocols. When other known high risk factors such as male sex, Caucasian race, and age are added, it is possible that a small enough high risk population can be identified that will make prevention of the later stages of the refluxadenocarcinoma sequence feasible.


1. Hayward J. The lower end of the esophagus. Thorax 1961;16:36-41.

2. Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett's esophagus. N Engl J Med 1976;295:476-480.

3. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825-831.

4. Jain R, Aquino D, Harford WV, Lee E, Spechler SJ. Cardiac epithelium is found infrequently in the gastric cardia. Gastroenterology 1998;114:A160.

5. Clark GWB, Ireland AP, Chandrasoma P, DeMeester TR, Peters JH, Bremner CG. Inflammation and metaplasia in the transitional epithelium of the gastroesophageal junction: a new marker for gastroesophageal reflux disease. Gastroenterology 1994;106:A63.

6. Oberg S, Peters JH, DeMeester TR, Chandrasoma P, Hagen JA, Ireland AP, Ritter MP, Mason RJ, Crookes P, Bremner CG. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. Ann Surg 1997;226:522-532.

7. Jamieson JR, Stein HJ, DeMeester TR, Bonavina L, Schwizer W, Hinder RA, Albertucci M. Ambulatory 24-hour esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility. Am J Gastroenterol 1992;87:1102-1111.

8. Chandrasoma PT, Der R, Ma Y, Dalton P, Taira M. Histology of the gastroesophageal junction; an autopsy study. Am J Surg Pathol 2000;24:402-409.

Publication date: August 2003 OESO©2015