Endoscopy 2006; 38(6): 652-653
DOI: 10.1055/s-2006-925455
Letter to the Editor
© Georg Thieme Verlag KG Stuttgart · New York

The Prevalence of Esophageal Cardiac Glands: Relationship with Erosive Esophagitis and Nonerosive Reflux Disease (NERD) in Japanese Patients

K.  Yagi1 , A.  Nakamura1 , A.  Sekine1 , H.  Umezu2
  • 1Dept. of Internal Medicine, Niigata Prefectural Yoshida Hospital, Niigata, Japan
  • 2Division of Pathology, Niigata University Medical and Dental Hospital, Niigata, Japan
Further Information

Publication History

Publication Date:
27 June 2006 (online)

Gastroesophageal reflux disease (GERD) can be classified into nonerosive reflux disease (NERD), erosive esophagitis, and Barrett’s esophagus [1]. NERD is defined as the presence of typical symptoms of GERD caused by intraesophageal acid, in the absence of endoscopically evident esophageal mucosal injury [2] [3]. The mechanism of NERD has been well studied [2] [3]. However, in a previous study we reported that yellow elevated areas in the distal squamous epithelium represent esophageal cardiac glands and that exposed esophageal cardiac glands are observed under magnification [4]. We read with great interest a recent review article describing esophageal cardiac glands [5].

Esophageal cardiac glands exist underneath the squamous epithelial layer in the distal esophagus [4] [5]. A relationship between esophageal cardiac glands and Helicobacter pylori infection has been reported [4]. The appearance of esophageal cardiac glands was observed more frequently in patients with H. pylori infection than in those without it [4]. NERD is also reported to be more frequent in H. pylori-positive patients than in those without H. pylori infection [1]. Although the role of esophageal cardiac glands has not been clarified, they may prevent injury to the squamous epithelium caused by acid reflux.

We ascertained whether or not the prevalence of esophageal cardiac glands differs between patients with erosive esophagitis and patients with NERD. Sixty-two patients (35 men, 37 women; median age 62.1 years) with erosive esophagitis or NERD underwent upper gastrointestinal endoscopy. All of the patients were asked if they had GERD symptoms more than twice a week and whether or not they were taking histamine2-receptor antagonists or proton-pump inhibitors before the endoscopic examination. Any patients who had been taking such drugs were excluded from the study. All of the patients consented to have biopsy specimens taken for histological examination before the endoscopic examination if they had erosive esophagitis. All of the patients who had GERD symptoms more than twice a week consented to have biopsy specimens taken for histological examination. In all of the patients with erosive esophagitis or/and GERD symptoms, the distal margin of the squamocolumnar junction was observed in order to ascertain whether or not a yellow elevated area was present. If it was, one biopsy specimen was taken from it. If no yellow elevated areas were observed, a specimen was taken from the distal side of the squamous epithelium for histological examination. In addition, four biopsy specimens from the gastric antrum and gastric body were taken to check for the presence of H. pylori by culture and histological examination.

The muscularis mucosa side of all of the biopsy specimens was stretched and fixed on filter paper, and the specimens were then bathed in 10 % formalin so that they could be divided vertically for analysis of the squamous epithelium and proper mucosal layer bearing esophageal cardiac glands. Sections cut from the paraffin blocks were subjected to hematoxylin-eosin and Giemsa staining. All of the specimens were examined and the findings were interpreted by a single pathologist (H.U.), who was unaware of the endoscopic findings.

If the culture was positive or if H. pylori was observed in the Giemsa-stained specimens, the patient was diagnosed as being H. pylori-positive. If the culture was negative and no H. pylori was observed in the Giemsa-stained specimens, the patient was diagnosed as being H. pylori-negative.

The chi-squared test for independence was used to evaluate the significance of sex differences, differences in the prevalence of histologically evident esophageal cardiac glands, and differences in the prevalence of hiatus hernia and H. pylori infection between patients with erosive esophagitis and patients with NERD. Differences were considered to be statistically significant at P < 0.05.

Endoscopic observation revealed yellow elevated areas, indicating the presence of esophageal cardiac glands, in the squamous epithelium of the distal esophagus (Figure [1]). Histologically, the esophageal cardiac glands were present in the proper mucosal layer and connected to the papillae of the squamous layer. The ducts of the glands were sometimes evident in the squamous layer (Figure [2]). The endoscopic appearance of the distal esophagus without the yellow elevated area is shown in Figure [3]. Males comprised 65.0 % of the patients with erosive esophagitis and 40.9 % of the patients with NERD, but the sex difference was not significant. Esophageal cardiac glands were histologically evident in 12.5 % of the patients with erosive esophagitis and 63.6 % of the patients with NERD, and the difference between the two groups was significant (P < 0.01) (Table [1]). Hiatus hernia was present in 77.5 % of the patients with erosive esophagitis and 59.1 % of the patients with NERD, but the difference between the groups was not significant. H. pylori infection was present in 30.0 % of patients with erosive esophagitis and 54.5 % of patients with NERD, and again the difference was not significant (Table [1]).

Table 1 Differences in baseline characteristics between patients with erosive esophagitis and patients with NERD (n = 62) Patients with erosive esophagitis(n = 40) Patients with NERD(n = 22) Age (years; mean ± SD) 63.2 ± 13.0 61.6 ± 12.8 Sex (n, %) Male * Female * 26 (65.0 %)14 (35.0 %) 9 (40.9 %)13 (59.1 %) Yellow elevated areas (n, %) Positive Negative 7 (17.5 %)33 (82.5 %) 18 (81.8 %)4 (18.2 %) Histologically evident esophageal cardiac glands, n (%) Positive ** Negative ** 5 (12.5 %)35 (87.5 %) 14 (63.6 %)8 (36.4 %) Hiatus hernia, n (%) Positive * Negative * 31 (77.5 %)9 (22.5 %) 13 (59.1 %)9 (40.9 %) Helicobacter pylori, n (%) Positive * Negative * 12 (30.0 %)28 (70.0 %) 12 (54.5 %)10 (45.5 %) * Not significant. ** P < 0.01. Chi-squared test for independence.

Figure 1 Endoscopic view of a yellow elevated area, indicating the presence of esophageal cardiac glands.

Figure 2 Histological features of esophageal cardiac glands. The gland ducts are present in the squamous layer.

Figure 3 Endoscopic view of the distal esophagus in a patient lacking a yellow elevated area indicating esophageal cardiac glands.

It is still unclear how esophageal cardiac glands function in the distal esophagus. This histological study indicates that esophageal cardiac glands may serve to protect the squamous epithelium against acid reflux. Marcinkiewicz et al. [6] reported that patients with NERD may have an esophageal secretory potential that could help prevent the development of erosive esophagitis. The presence of esophageal cardiac glands may serve this function, although further research is needed to confirm this.

Martinez et al. [7] divided 71 patients with NERD into two groups - 32 patients with an abnormal pH test result and 39 patients with a normal pH test result. They found that the lack of esophageal mucosal breaks in NERD patients with abnormal pH was probably due to the preservation of local mucosal defensive mechanisms [7]. However, there have been no reports of any clear defensive mechanisms that protect squamous epithelium against acid. Our finding that esophageal cardiac glands were present significantly more often in NERD patients than in patients with erosive esophagitis does not contradict the theory that esophageal cardiac glands protect squamous epithelium against acid reflux.

In summary, NERD patients have a significantly higher prevalence of esophageal cardiac glands than patients with erosive esophagitis. These results suggest that esophageal cardiac glands may therefore function to preserve local mucosal defense mechanisms.

Competing interests: None

References

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K. Yagi, M. D. 

Dept. of Internal Medicine
Niigata Prefectural Yoshida Hospital

Tsubame-city
Niigata-ken 959-0242
Japan

Fax: +81-256-92-2610

Email: yagikazu@pop12.odn.ne.jp

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