Journal of Gastroenterology and Hepatology (1995) 10,331-333

ALIMENTARY TRACT AND PANCREAS

Barrett’s oesophagus and Helicobacter pylori

ZAIGHAM ABBAS, AKBAR S. HUSSAINY,‘ FARHAT IBRAHIM, S. M. WASIM JAFRI, HIZBULLAH SHAIKH’ AND A. HALEEM KHAN

Departments of Medicine and ‘Pathology, The Aga Khan University Hospital, Karachi Pakistan

Abstract In order to demonstrate the presence of Helicobucter pylon’ in the metaplastic epithelium of Barrett’s oesophagus and to evaluate its possible association with this entity, we examined 29 cases of Barrett’s oesophagus where concomitant antral biopsies were also available. These cases were compared with an equal number of age and sex matched controls of uncomplicated reflux oesophagitis. H. pylori was present in 11 of 29 cases of Barrett’s oesophagus (38%). No increase in the frequency of H. pylon’ antral gasmtis was found in patients of Barrett’s oesophagus compared to the control group of uncomplicated reflux oesophagitis. The positivity of Barrett’s oesophagus for H. pylon’ correlated with the presence of H. pylm’ antral gasmtis (P < 0.05), although in two cases of H. pylon*-positive Barrett’s oesophagus antral biopsies were negative for H. pylori. No difference was found in the severity of inflammatory and dysplastic changes of H. pylori- positive and H. pylmi-negative Barrett’s oesophagus. Presence of H. pylari does not seem to alter the natural history of Barrett’s oesophagus.

Key words: Barrett’s oesophagus, HeZicobacter j~jd~ti, reflux oesophagitis.

INTRODUCTION

Barrett’s oesophagus’ is a pathological condition charac- terized by metaplastic replacement of normal squamous epithelium of distal oesophagus by columnar epithelium of a heterogeneous variety? It is a recognized complication of gastrooesophageal reflux disease3 and has a malignant potential.4,’ Helicobucter pylon‘ is frequently found splayed along the gastric mucosa and its infection is strongly associated with antral (type B) g a ~ m t i s . ~ ~ ~ The organism also infects the areas of gasmc metaplasia of duodenum.*,9 We examined cases of Barrett’s oesophagus to demonstrate the presence of H. pylon’ in t h i s metaplastic epithelium and to evaluate its possible implications.

METHODS

Between January 1991 and June 1993, 1072 oesophageal biopsies were taken from patients presented to the Adult Gastroenterology Service of The Aga Khan University Medical Centre. Diagnosis of Barren’s oesophagus was made in 40 cases. This analysis was carried out on 29 cases which Willed the following criterk (i) the endoscopic and biopsy evidence of h t t ’ s oesophagus; (ii) con- mmitant antral biopsy specimens were available; and (iii) these patients had not received any antihelicobacter treat-

ment. Endoscopy records were reviewed to confirm the presence of columnar epithelium in the tubular oesophagus and to exclude hiatus hernia. Barrett’s oesophagus was defined endompically as presence of velvety red mucosa in the distal oesophagus extending above the lower oesophageal sphincter either circumferentially for 3 cm or as tongues or islands. Oesophagitis was defined as presence of hyperaemia, erosions or ulcerations. Evidence of any antd hyperaemia was recorded.

At least three biopsies were obtained from the Barrett’s oesophagus and two from antrum. Biopsy sections were stained with haematoxylin and eosin (H&E) for routine histology and modified Giemsa’s stain for the detection of H. pylon.. Specimens were reviewed by two experienced histopatholgists. The sensitivity of diagnosis of H. pylon. by these histopathologists was evaluated. It was found to be comparable to the rapid urease test (89 ‘us 84%). The Barrett’s oesophagus was categorized into three epithelial types:

(1) F u n d epithelium: gastric fundus like epithelium with pits, mucous glands, parietal and chief cells. (2) Junctional epithelium: similar to that of cardia with

pits and mucous glands but no parietal or chief cells. (3) Specialized columnar epithelium: similar to that

of s d bowel with villiform surface, mucous glands and intestinal type of goblet cells. One or more types could be recognized in a given specimen.

Correspondence: Dr Zaigham Abbas, The Aga Khan University Hospital, Karachi, Pakistan. Accepted for publication 5 August 1994.

332 Z. Abbus et al.

The presence and degree of dysplasia and inflammation in the columnar and squamous epithelium was recorded. Degree of inflamma tion was graded according to the criteria of Paull et ul.” Typical curved bacilli were identified on H&E and Giemsa’s stain. Antral biopsies of the cases were also reviewed for the H. pylm’ infection. Our cases of Barren’s oesophagus were then compared with an equal number of age and sex matched controls. These controls comprised of patients without Barrett’s oesophagus but who had endoscopic and histological evidence of oesophagi- tis. This group was selected prospectively and was screened for H. pylori antral infection by histology and rapid urease test. The prevalence of H. pyluri infection was then com- pared among the two groups (Barrett’s vs uncomplicated oesophagitis). Data were then analysed using Chi-square with Yates’ correction. A P value of < 0.05 was considered as statistically significant.

RESULTS The patients with Barrett’s oesophagus ranged in age from 24 to 80 years with a median age of 45 years. Eighteen of these patients were male and 11 female. The biopsies revealed junctional type of epithelium as the most frequent type (59%) followed by gastric fundal type (41%) and specialized columnar type (17%). More than one epithelial type was seen in some specimens. Dysplasia was an infre- quent observation. It was noted in only three patients. However, the inflamma tory changes were present in a signi- ficant number of cases (97% inflammation of columnar epithelium vs 83% inflammation of adjacent squamous epithelium; Table 1). Most of these inflamma tory changes were of mild to moderate intensity. H. pylon’ were identified in the fundal and junctional types of gastric metaplastic epithelium in 11 cases (38%). H. pylm* antral gastritis was present in 14 cases of Bafiett’s oesophagus (48%) and 18 cases of control uncomplicated reflux oesophagitis (62%) and there was no statistically sigdkant difference amongst the two groups. In the cases of Barrett’s oesophagus, posi- tivity for H. pylon’ correlated with the presence of H. pylm. antral gasmtis (P < 0.05). In nine of 11 (82%) cases of H. pylm’-positive Barrett’s oesophagus, H. pylon’ could be identified in the a n d biopsies (M five of 18 [28%] for H. pylon-mgative Barren’s). Comparison of cases of H. pylori-positive and H. pylon-negative Barrett’s oesophagus is given in Table 2.

Table 1 Histological features of Barren’s oesophagus

Junctional type epithelium Gastric fundic type epitheliutn Specialized columnar epithelium D ysplasia Idlammation of columnar epithelium Inflammation of adjacent squamous epithelium

Helicobacter positivity

n 9 6

More than one epithelial type in some specim-.

Table 2 Comparison of patients of Barren’s oesophagus with and without Helicobacrer pylon infection

H. pylon presence Factor Yes No

(n = 11) (n = 18)

Sex (WF) 417 14/4

Median 45 45 Range (24-80) (28-77)

Age (Years)

Type of infected epithelium Junctional 5 12

Dysplasia 0 3 H. pyhi antral gastritis’ 9 5 Inflammation of columnar epithelium

Fundal 6 6

Absent 0 1 Grade I 4 8 Grade I1 6 6 Grade I11 1 3

Absent 1 4 Grade I 6 8 Grade I1 4 4 Grade I11 0 2

Inflammation of squamous epithelium

‘P value < 0.05.

DISCUSSION H. pylon. were present in 11 cases (38%) of Barrett’s oesophagus. Presence of H. pylon‘ in Barren’s oesophagus raises issues such as the following: (i) What is the source of H. pylon? (ii) Does persistent H. pylor’ antral gastritis lead to infection of distal oesophagus with H. pylon’ and metaplastic changes in the distal oesophagus? (iii) Does persistent H. pylon‘ infection of Barren’s oesophagus lead to mutagenic process? (iv) Would the eradication of H. pyhireverse some of the dysplastic changes in the Barrett’s

Forty-eight per cent of cases of Barrett’s oesophagus and 62% of cases of uncomplicated reflux oesophagitis were harbouring H. pylori in their antrum. The presence of H. pylon’ in Barren’s oesophagus correlated with the presence of these organisms in the antrum (P < 0.05). It is possible that chronic reflux results in migration of H. pylon* from the antrum to the distal oesophagus. In two cases, H. pylon’ was present in Barrett’s oesophagus but absent in antral biopsies. In these cases, H. pylon’ might have been missed in the specimens due to patchy distri- bution of these organisms.” The other possibility is that the metaplastic epithelium of Barren’s oesophagus in these cases was colonized in an antegrade fashion before the establishment of infection in the antrum.

The prevalence of H. pylm‘ and antral gastritis in the Pakistani community is unknown, although in a study carried out on dyspeptic patients of Karachi, 84.6% cases of duodenal ulcer were positive for H. pylori infection.’* H. @hi infection of antrum leads to gastric hypersecretion” which in turn results in gastric metaplasia of duodenal

oesophagus?

Barrett 's oesophagus and H. pylori 333

epitheli~m.'~ H. pylon' now colonizes the metaphstic

a similar mechanism also operate in cases of gastroeso- phageal reflux disease resulting in Barren's oesophagus?

There was no increase in the incidence of H. pylori antral gastritis in patients of Barrett's oesophagus compared with the uncomplicated reflux oesophagitis. Similar to our study Blaser et hl. have failed to demonstrate association of Barrett's oesophagus with the H, pylon' antral gasmti~. '~ We could not find any relation between the degree of idammation and the presence of H. pylon. in Barrett's oesophagus as suggested by P a d and Yardley.16 It appears that gastro-oesophageal reflux is the main inciting and ongoing injurious factor in the pathogenesis of Barrett's oesophagu~'~ and the presence of H. pylon' in the oesopha- gus of patients with Barrett's oesophagus is probably secondary to its presence in the stomach.'8

H. pylon. inflammation of the stomach induces several mutagenic processes including cellular proliferation, possibly by increased production of epidermal growth factor and damage to DNA by neutrophil produ~ts. '~ Association has been reported between high gastric caner rates and H. pylon' infection20*2' and there is a report of reversal of gastric dysplasia with antihelicobacter therapy.22 Does the infection of Barren's oesophagus with H. pylon. start a similar mutagenic process? Further studies are needed to determine whether antihelicobacter treatment along with anti-reflux therapy would reduce the risk of carcinoma development in Barrett's oesophagus.

epithelium to start the process of inflamma ti0n.9~4 DWS

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