Helicobacter pylori colonization of Barrett's esophagus and its progression to cancer

Helicobacter pylori (HP) plays a crucial role in gastric carcinogenesis. Few studies have looked at the relationship between HP and Barrett's esophagus/cancer. To further investigate this, a study comparing the prevalence of HP and increasing grades of dysplasia was undertaken. Biopsies from 19 malignant and 94 benign cases of Barrett's esophagus were analysed histologically for the presence of HP. 34% of non-dysplastic Barrett's epithelium was colonized with HP compared with only 17% of dysplastic/malignant cases (P = 0.04). No relationship was found between HP status and: (i) length of Barrett's esophagus; (ii) the presence of ulcers or strictures; and (iii) previous anti-reflux surgery. HP colonization of Barrett's esophagus is not uncommon. We found that HP has a negative correlation with increasing dysplasia which is analogous to gastric carcinogenesis. This finding should be investigated in prospective studies to elucidate its role in Barrett's adenocarcinoma.     

Barrett's esophagus

The columnar replacement of squamous epithelium in the lower esophagus is the result of gastroesophageal reflux. Whether the squamous cells are replaced or undergo metaplasia is still conjectural. This neoepithelium is unstable in the presence of continued reflux and prone to complications of stricture, ulceration, and adenocarcinoma. Considerable evidence supports the hypothesis that duodenal contents play a role in the development of Barrett's esophagus and its complications. The increasing incidence of adenocarcinoma in Barrett's esophagus is of concern in the Western World. Surveillance programs in some centers have been successful in early diagnosis, and excellent survival periods have been reported following resection in these cases. Both medical and surgical antireflux treatment is successful in symptom relief, but even in the absence of symptoms, reflux may continue. Surgery offers better overall results than proton pump inhibition of gastric acid and has been more popular since less aggressive (minimally invasive) techniques have been popularized. Mucosal ablation and antireflux measures by medicine or surgery are still in the experimental stages but hold considerable promise for the future.     

Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.     

Barrett's esophagus: a review

Complications of Barrett's esophagus include ulceration, stricture, hemorrhage, perforation, and the development of malignancy. Barrett's esophagus and adenocarcinoma may be diagnosed simultaneously and that gastroesophageal reflux symptoms may be absent in many cases. Although endoscopic surveillance is justified, no agreement on the frequency can be made. Survival of patients with adenocarcinoma in Barrett's esophagus depends on the stage at diagnosis.     

Acid, protons and Helicobacter pylori

The anti-ulcer drugs that act as covalent inhibitors of the gastric acid pump are targeted to the gastric H+/K+ ATPase by virtue of accumulation in acid and conversion to the active sulfenamide. This results in extremely effective inhibition of acid secretion. Appropriate dosage is able to optimize acid control therapy for reflux and peptic ulcer disease as compared to H2 receptor antagonists. However, clinical data on recurrence show that Helicobacter pylori eradication should accompany treatment of the lesion. These drugs have been found to synergize with many antibiotics for eradication. The survival of aerobes depends on their ability to maintain a driving force for protons across their inner membrane, the sum of a pH and potential difference gradient, the protonmotive force (pmf). The transmembrane flux of protons across the F1F0 ATPase, driven by the pmf, is coupled to the synthesis of ATP. The internal pH of H. pylori was measured using the fluorescent dye probe, BCECF, and the membrane potential defined by the uptake of the carbocyanine dye, DiSC3 [5] at different pHs to mimic the gastric environment. The protonmotive force at pH 7.0 was composed of a delta pH of 1.4 (-84mV) and a delta potential difference of -131mV, to give a pmf of -215 mV. The effect of variations in external pH on survival of the bacteria in the absence of urea correlated with the effect of external pH on the ability of the bacteria to maintain a pmf. The effect of the addition of 5 mM urea on the pmf was measured at different medium pH values. Urea restored the pmf at pH 3.0 or 3.5, but abolished the pmf at pH 7.0 or higher, due the production of the alkalinizing cation, NH3. Hence H. pylori is an acid-tolerant neutrophile due to urease activity, but urease activity also limits its survival to an acidic environment. These data help explain the occupation of the stomach by the organism and its distribution between fundus and antrum. This distribution and its alteration by proton pump inhibitors also explains the synergism of proton pump inhibition and antibiotics such as amoxicillin and clarithromycin in H. pylori eradication.     

The surgical management of Barrett's esophagus

Barrett's esophagus is an increasing health concern in most Western countries. The diagnosis is usually made during investigation of patients with symptoms of gastroesophageal reflux disease. The appropriate antireflux procedure, performed in properly selected patients, provides long-term symptomatic relief in 80% to 90% of patients. The effect of reliable and complete control of gastroesophageal reflux on the natural history of Barrett's metaplasia once it has developed and on its prevention in symptomatic patients who have not yet developed Barrett's changes is one of the most important areas of study over the next decade.     

The histologic spectrum of Barrett's esophagus

To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.     

Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus

OBJECTIVES: Barrett's esophagus is associated with adenocarcinoma of the cardia and esophagus, regardless of its extent. The aim of this study was to compare the prevalence and incidence of dysplasia and adenocarcinoma in short segment and traditional long segment Barrett's esophagus. METHODS: Seventy-four patients with short segment Barrett's and 78 with traditional Barrett's entered the study. RESULTS: There were no significant differences in age or gender between the two groups of patients with Barrett's esophagus. A greater percentage of patients with short segment barrett's were black (p = 0.04). The prevalence of dysplasia at diagnosis in patients with short segment Barrett's was 8.1% versus 24.4% in patients with traditional Barrett's (p < 0.007). Adenocarcinoma was noted at diagnosis only in patients with traditional Barrett's (p < 0.0005). Twenty-six patients with short segment Barrett's and 29 with traditional Barrett's were followed prospectively for 12-40 months. Dysplasia developed during follow-up in two patients with short segment Barrett's and in six patients with traditional Barrett's (p < 0.05). Neither high grade dysplasia nor cancer developed in any patients with short segment Barrett's. High grade dysplasia did develop in two patients with traditional Barrett's esophagus, and mucosal adenocarcinoma developed in one. The frequency of dysplasia on the latest surveillance examination continued to be significantly higher for patients with traditional Barrett's (p = 0.03). Follow-up surveillance biopsy specimens of Barrett's mucosa frequently demonstrated an absence of goblet cells in patients with short segment Barrett's compared with patients with traditional Barrett's (p < 0.0001). CONCLUSIONS: The prevalence of dysplasia or adenocarcinoma and the incidence of dysplasia in patients with traditional Barrett's esophagus are significantly higher than in patients with short segment Barrett's esophagus. Further prospective surveillance is required to determine whether the incidence of adenocarcinoma in patients with short segment Barrett's esophagus is significantly lower.     

Helicobacter pylori in children

Helicobacter pylori is the major cause of antral gastritis in children, however, it is not always associated with symptoms. The exception to this occurs in duodenal ulcer disease with which H. pylori is linked in children albeit less strongly than in adults. Duodenal ulcers do not recur in older children following eradication of H. pylori. The importance of asymptomatic carriage of H. pylori in children, particularly in relation to the duration of this infection and the subsequent development of gastric cancer, remain to be established. Helicobacter pylori is associated with both hypochlorhydria and persistent diarrhoea in children in developing countries, but the significance of this association is still unknown. Although there is no consensus on the optimal regimen for treating H. pylori infection in children, dual therapy with amoxycillin and bismuth subcitrate for 2 weeks followed by monotherapy with bismuth subcitrate for a further 6 weeks will eradicate H. pylori infection in the majority of children. Those who relapse may be treated with a repeat course plus metronidazole for 4 weeks. Compliance with such regimens is a problem and shorter treatment courses that are equally effective in children need to be defined. Similarly, studies are required on the influence of the intrafamilial reservoir of H. pylori infection on relapse after treatment and the need for whole family eradication therapy.     

Helicobacter pylori in 1997

In this review Helicobacter pylori (H. pylori) infection and its relation to different diseases is presented. H. pylori doesn't cause inconvenience to most infected people, though all infected persons have chronic active gastritis. The 10 year risk of peptic ulcer for people infected with H. pylori is about 10%. Randomized double-blinded trials have shown that eradication of H. pylori can cure most patients with peptic ulcer disease. Some people infected with H. pylori develop atrophic gastritis which is a risk factor for development of gastric cancer. It is not known if H. pylori screening and eradication would have a prophylactic effect against gastric cancer. It is also unknown if persons with non-organic dyspepsia and persons in long-term treatment with proton-pump-inhibitors would benefit from H. pylori eradication.     

Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study

OBJECTIVES: In Barrett's esophagus, early adenocarcinomas are often missed on endoscopic biopsy. We therefore examined the distribution and extent of dysplasia and carcinoma in the resected esophagus for comparison with the preoperative biopsy findings. METHODS: Patients whose endoscopy showed Barrett's esophagus but no visible cancer had four-quadrant esophageal biopsies taken every 2 cm. After resection for high-grade dysplasia or early adenocarcinoma, the esophagus was mapped histologically. RESULTS: Nineteen patients had surgery for high-grade dysplasia; two of them (10.5%) had adenocarcinoma in the resected esophagus. Eleven patients had resection after a biopsy diagnosis of adenocarcinoma or suspicion of adenocarcinoma. Esophagectomy mapping confirmed carcinoma in only five of them. Median surface areas were: total Barrett's esophagus 32 sq cm, low-grade dysplasia 13 sq cm, high-grade dysplasia 1.3 sq cm, adenocarcinoma (seven cases) 1.1 sq cm. CONCLUSIONS: Areas of high-grade dysplasia and microscopic carcinoma in Barrett's esophagus are often small. Biopsy differentiation between these lesions is difficult. A systematic endoscopic biopsy protocol will reduce the chance of missing early malignancy in Barrett's esophagus.     

Helicobacter pylori, gastric pathology, and histopathological diagnosis

Structural analogues of ZAPA, Z-3-[(aminoiminomethyl)thio]prop-2-enoic acid, an isothiouronium analogue of GABA, are potent GABAA agonists as seen in the isolated guinea-pig ileum and in the facilitation of [3H]diazepam binding to rat brain membranes. Compounds with guanidino or amidine groups replacing the amino functionality of GABA were also found to be active. The highest activity was displayed by the isothiouronium salts in which the conformational flexibility of the molecule is restricted by a Z-substituted carbon-carbon double bond. A series of bis-isothiouronium compounds was prepared from aliphatic alpha, omega-bis-thioureas as mixtures of E and Z adducts. Maximum GABAA agonist activity for this series was found with a C6-C8 carbon chain, and the results were consistent with an interaction at the GABAA receptor with only one end of the molecule, rather than the more potent effect expected of a molecule bridging two active sites. GABAA antagonist/partial agonist activity was observed on the guinea pig isolated ileum for a number of different analogue types, with the most potent being bis-isothiouronium derivatives. None of the substituted derivatives of ZAPA was as active as ZAPA itself, and maximum GABAA activity was found in the n-pentyl and n-hexyl analogues.     

Morphology of Barrett's esophagus and Barrett's-associated dysplasia and adenocarcinoma

This article has reviewed the morphologic features of BE and its complications of dysplasia and adenocarcinoma in routinely processed endoscopic biopsy and resection specimens. In addition, the problems related to the diagnosis of dysplasia in tissue samples have been analyzed, and the role of esophageal brush cytology in the diagnosis of these lesions has been reviewed.     

Duodenal ulcer, Helicobacter pylori, and gastric secretion

Patients with chronic dyspepsia were categorised by macroscopic appearance at oesophagogastroduodenoscopy as having duodenal ulceration (DU), other diagnosed lesions such as reflux oesophagitis, carcinoma of stomach, etc, or no organic lesion (non-ulcer dyspepsia, NUD). Material was collected to identify gastric infection with Helicobacter pylori (H pylori) by CP urease test, culture, and histological examination and to make the microscopic diagnosis of active chronic gastritis. Each patient in the DU and NUD categories was then invited to volunteer for a gastric secretion study in which maximal gastric secretion in response to histamine was measured. Sixty two gastric secretion tests were performed (31 DU, 31 NUD). The presence of H pylori was associated with active chronic gastritis (100%). DU patients secreted more acid than the NUD patients. H pylori positivity was associated with decreased maximal gastric secretion in both groups. There was a positive correlation between smoking and maximal acid output shown only in H pylori negative but not in H pylori positive patients. These findings were clear cut when all corrections of maximal gastric secretion were made for pyloric loss, duodenogastric reflux, and stature. This study failed to show any aetiological link between H pylori and DU by increased maximal gastric secretion.