Ulcers and gastritis

This article reviews recently published reports on ulcers and gastritis. Helicobacter pylori is known to be an important pathogen involved in gastroduodenal inflammation and peptic ulcers. Conventional endoscopy is of limited usefulness in the evaluation of gastritis, but magnifying endoscopy is evidently helpful in the diagnosis of chronic atrophic gastritis, intestinal metaplasia, and H. pylori infection. A significant reduction in the incidence of refractory ulcers and the prevalence of H. pylori infection in patients with peptic ulcer disease followed the introduction of H. pylori eradication treatment. Chronic H. pylori infection is associated with gastric cancer, and the effect of H. pylori eradication on the prevention of gastric cancer is an important issue that is still a matter of controversy. Endoscopic hemostasis and intravenous proton-pump inhibitor (PPI) infusion represent a widely accepted approach to the treatment of peptic ulcer bleeding. In clinical practice, it is important to prevent recurrent bleeding and to treat patients who do not respond to endoscopic therapy or PPI treatment. Laparoscopic repair for peptic ulcer perforations, with postoperative eradication treatment, has gradually met with acceptance in patients with H. pylori infection. H. pylori infection and its treatment continue to be interesting problems in this field.     

Ulcer and gastritis

As in previous years, developments in the field of ulcers and gastritis have been dominated by new findings related to Helicobacter pylori. With the decrease in the frequency of H. pylori infection, the relative proportion of non-H. pylori ulcers has increased. Attempts to reduce the endoscopy workload by H. pylori or CagA screening have not been successful, and are probably ill-advised. It has become increasingly clear that curing H. pylori infection will not automatically lead to complete relief of symptoms in patients with duodenal ulcer disease. Post-therapy confirmation of cure will probably become the norm. Studies comparing omeprazole to misoprostol or ranitidine for nonsteroidal anti-inflammatory drug (NSAID) ulcer prevention in true NSAID ulcers have shown that omeprazole is equal to full-dose misoprostol for ulcer healing and to the lowest useful dose of misoprostol for ulcer prevention. H2-receptor antagonists cannot be recommended for NSAID ulcer healing or prevention. Elimination of H. pylori increases the prevalence of gastroesophageal reflux disease in a population in such a way that superficially, there appears to be a choice between more gastroesophageal reflux disease or multifocal atrophic gastritis. The risk of developing adenocarcinoma of the esophagogastric junction is many times (10-fold to 60-fold) less than the risk of developing gastric cancer from CagA-positive H. pylori infection with multifocal atrophic gastritis - the "protective" lesion.     

Ulcer and gastritis

The literature on peptic ulcer and gastritis in 2000 again focused on the topics of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and gastric cancer. New diagnostic tests for H. pylori infection have been evaluated, and rescue therapies for failed H. pylori eradication have been tested. The causal relationship between H. pylori infection and nonulcer dyspepsia, gastric cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated topics of debate. In 2000, landmark clinical trials and meta-analyses were published addressing these issues. The role of endoscopy in managing nonulcer dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin users was reexamined in high-risk patients. Clinical benefit was finally confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium year turned out to be a very important one in the advancement of knowledge in this field.     

Ulcer and gastritis

Recent progress in the area of ulcer and gastritis is still dominated by findings and reports on Helicobacter pylori and nonsteroidal anti-inflammatory drugs, which in turn are the two major causes of peptic ulcers. Although the prevalence of H. pylori is declining in most developed countries, it is still contributing to a significant proportion of peptic ulcers globally. The interrelationship of H. pylori gastritis in patients with gastroesophageal reflux has become more apparent. H. pylori-induced gastric body gastritis is associated with reduced acid production, and thus with reduced reflux and esophagitis. The controversies regarding the interactions between H. pylori and NSAIDs have still not been settled. With the availability of the new COX-2-specific inhibitors, the current scenario of NSAID-related gastroduodenal complications will certainly change. Short-term usage of these agents has significantly reduced the incidence of endoscopic ulcers, but the benefits in terms of clinical outcomes, such as bleeding or perforation, remain to be determined. This review summarizes the recent literature on peptic ulcer and gastritis.     

Causal relationship between Helicobacter pylori infection and upper gastroduodenal diseases

Helicobacter pylori infection causes chronic gastritis (nonatrophic gastritis), which progresses to atrophic gastritis and intestinal metaplasia over a period of decades. Atrophy may result from inflammation and apoptosis caused by H. pylori infection. H. pylori is an important risk factor for peptic ulcer disease. Duodenitis in the gastric metaplasia of the duodenum, hypergastrinemia, and impaired proximal duodenal mucosal bicarbonate secretion are considered causal factors for duodenal ulcer disease. Low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) develops in response to H. pylori infection. Studies of Mongolian gerbil model demonstrated that H. pylori had an initiator or promoter effect on gastric carcinogenesis.     

Role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drug (NSAID) are independent risk factors for peptic ulcers and ulcer complications and they have additive or synergistic effects. A meta-analysis showed that the OR for the incidence of peptic ulcer was 61.1 in patients infected with H. pylori and also taking NSAID when compared to patients uninfected with H. pylori and not taking NSAID. H. pylori eradication may prevent NSAID-induced ulcers in NSAID naive patients. In patients receiving long-term NSAID, proton pump inhibitor(PPI) is more effective in the prevention of ulcer recurrence and bleeding. However, H. pylori eradication should be considered in patients receiving long -term PPI maintenance treatment to prevent the development of corpus gastritis and gastric atrophy.     

Pathogenesis of gastric and duodenal ulcer in the elderly

In the elderly, H. pylori infection and nonsteroidal anti-inflammatory drug(NSAID) use are most important risk factors for peptic ulcer disease. It is now recognized that, in patients with H. pylori infection, nonatrophic antral-predominant gastritis results in increased acid secretion, which is seen in duodenal ulcer patients, whereas corpus-predominant gastritis and pangastritis result in decreased acid secretion, that are seen in patients with proximal gastric ulcer and gastric cancer. These physiological changes are considered to be related to disease outcome. On the other hand, NSAIDs induced gastrointestinal toxicity is primarily due to the inhibition of mucosal prostaglandin synthesis in the gastric mucosa, which subsequently impairs the gastric cytoprotective factors. These two factors may independently, or even synergistically, cause the development of peptic ulcer disease in the elderly.     

Helicobacter pylori associated antral gastritis in peptic ulcer disease patients and normal healthy population of kashmir, India

Aim: To study the association of Helicobacter pylori infection with chronic antral gastritis in peptic ulcer disease patients and healthy population of Kashmir.Methods: 50 peptic ulcer patients (duodenal ulcer = 46, gastric ulcer = 2 and combined duodenal and gastric ulcer = 2) and 30 asymptomatic healthy volunteers were included in this study. Peptic ulcer was diagnosed on endoscopic examination. 4-6 punch biopsies were taken from gastric antrum in all the individuals and in case of gastric ulcer an additional biopsy was taken from the edge of the ulcer to exclude its malignant nature. Helicobacter pylori (H. pylori) organism was diagnosed using three different test methods, viz. Histology (using Giemsa Stain), Microbiology (Gram Stain) and Biochemistry (using one minute Endoscopy Room Test). Histological diagnosis of H. pylori was taken as the "gold standard" for the presence of H. pylori organism. Histological diagnosis of gastritis was made using Hematoxylin and Eosin Stain and the gastritis was classified as active chronic gastritis and superficial chronic gastritis.Results: Out of 30 peptic ulcer disease patients with associated antral gastritis, 27 (90%) were positive for H. pylori on histological examination (13 superficial chronic gastritis and 14 active chronic gastritis) whereas out of 8 healthy volunteers with histological evidence of chronic antral gastritis, H. pylori was observed in 7 individuals (87.50%) (4 active chronic gastritis and 3 superficial chronic gastritis).Conclusion: A highly significant association between H. pylori infection with chronic antral gastritis both in peptic ulcer disease patients and healthy volunteers of Kashmir was found in this study. Association between H. pylori infection and chronic gastritis was 90% in peptic ulcer group and 87.50% in healthy population (P<0.005).     

HELICOBACTER PYLORI PREVALENCE IN A ROUTINE UPPER GASTROINTESTINAL ENDOSCOPY POPULATION

SUMMARY The presence of Helicobacter pylori (HP) in gastric biopsy specimens of 500 patients referred for routine upper gastrointestinal endoscopy for various abdominal complaints was investigated histologically and microbiologically. HP was detected in 429 of the 500 patients (86%). Antral biopsy specimens revealed gastritis in 457 out of 500 cases (91.4%). In the 43 patients who had normal histological findings, only 3 had HP infection (7%). The prevalence of HP in the patients with gastric and duodenal ulcers was 91%. In 95.6% of the ulcer patients, biopsy specimens showed gastritis. There was a statistically significant rise in the prevalence of HP with age. The correlation between histologic and microbiologic diagnostic methods was good. This study shows that HP positivity and gastritis are common in a routine endoscopy population and that there is a strong association between H. pylori, gastritis and peptic ulcer disease.     

Guidelines in the management of Helicobacter pylori infection in Japan--in comparison with the guidelines published in other countries

Helicobacter pylori(H. pylori) is a causative agent for chronic gastritis and is an important risk factor for peptic ulcers, gastric carcinomas, and gastric MALT lymphomas. In 2000, the Japanese Society for Helicobacter Research published a guideline on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. In this guideline, H. pylori eradication therapy is recommended in gastric or duodenal ulcer patients. H. pylori eradication is also recommended in gastric MALT lymphoma patients but the guideline says it should be done at specialist institutions. Considering the high prevalence of gastric carcinomas in Japan. H. pylori eradication for the prevention of gastric carcinomas should be discussed urgently.     

Future for basic and clinical studies on peptic ulcer disease

Since the discovery of H. pylori, various causes of peptic ulcer disease is reevaluated, and only four factors are now considered most important; H. pylori infection, gastric acid, NSAID administration, and mental and physical stress. Among them, gastric acid is an aggravating factor, and gastric acid alone can hardly develop peptic ulcers. The relationship between H. pylori infection and stress has been studied at Hanshin-Awaji great earthquake occurred in 1995. Immediately after the earthquake, the number of patients with peptic ulcer disease has been greatly increased, and those patients were considered to be typical cases of stress ulcers. Interestingly, however, it was found that 83.2% of the patients were infected with H. pylori. The data suggested that stress ulcer developed in those infected with H. pylori. In contrast, the relationship between H. pylori infection and NSAID in the development of ulcer disease is more complex. It is still unclear whether H. pylori infection is an additive effect for development of peptic ulcer disease by NSAID administration or not.     

Indication of H. pylori eradication therapy

In the guideline, for H. pylori the Japanese Society of Helicobacter published diagnosis and treatment in July 2000. Only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. In addition, Japanese social security foundation approves only peptic ulcers for indication of H. pylori eradication treatment. However, eradication therapy for atrophic gastritis should be considered in aspect of decreasing gastric cancer risk. Since accumulated epidemiological, experimental and clinical data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer should be included for a target eradication therapy. Indication of the treatment should be expanded to histological gastritis caused by H. pylori in our country, where prevalence of gastric cancer is very high.     

Esophagitis, gastritis and duodenitis provoked by cure of Helicobacter pylori infection

It has been recently reported that curing Helicobacter pylori (H. pylori) infection may provoke reflux esophagitis. We studied the effect of cure of H. pylori infection on the development of disorders of the upper gastrointestinal (UGI) tract. The estimated incidence of reflux esophagitis, gastric erosions and duodenal erosions after cure of infection was 8.9%, 32.8% and 8.9%. The incidences of reflux esophagitis, gastric erosions and duodenal erosions were 10.0%, 30.0% and 6.7% in patients with gastric ulcer, 2.8%, 36.1% and 27.8% in those with duodenal ulcer and 9.2%, 30.3% and 1.3% in those with atrophic gastritis. Therefore, patients whose H. pylori infection has been cured should carefully be investigated by endoscopy for H. pylori-associated disease.     

长春地区慢性胃病患者幽门螺杆菌感染状况调查

目的通过对本地区慢性胃病患者幽门螺杆菌（H.pylori）感染状况调查,了解本地区流行病学特点,为进一步阐明其与慢性胃病发生发展的关系提供理论依据。方法采用ELISA方法测定血清H.pyloriIgG抗体及CagA抗体;采取胃粘膜活检组织进行快速尿素酶试验,调查H.pylori感染情况,分析其与各种疾病的关系。结果1180例慢性胃病患者H.pylori感染率为67.11%,复合性溃疡、十二指肠溃疡、胃溃疡及慢性萎缩性胃炎感染率分别为90.9%、84.57%、83.96%和80.24%。与慢性浅表性胃炎相比差异有显著性。消化性溃疡、慢性萎缩性胃炎、胃癌和胃息肉患者血清Hp-CagA抗体的阳性率明显高于慢性浅表性胃炎（P〈0.05）。结论本地区慢性胃病患者H.pylori感染率高与多数地区的普通人群,H.pylori感染者尤其是CagA阳性者,更易发生慢性萎缩性胃炎、消化性溃疡及胃癌。     

Mucosal protective effects of ecabet sodium: pepsin inhibition and interaction with mucus

Pepsin, acid and Helicobacter pylori are major factors in the pathophysiology of peptic ulcer disease and reflux oesophagitis. Ecabet sodium reduces the survival of H. pylori in the stomach and inhibits pepsin activity in the gastric juice of experimental animals. Here we have investigated the effects of ecabet sodium on some of the factors involved in the dynamics of the mucosal barrier, i.e. pepsins and mucins. This study used gastric juice obtained from 12 non-symptomatic volunteers and nine patients with reflux oesophagitis. Ecabet sodium significantly inhibited pepsin activity in human gastric juice, with a maximum inhibition of 78%. Pepsin 1, the ulcer-associated pepsin, was inhibited to the greatest extent. The ability of gastric juice to digest mucin was significantly inhibited by ecabet. As with gastric juice proteolytic activity, the inhibitory effect of ecabet on mucolysis was greater in gastric juice from patients with reflux oesophagitis than in that from controls. Ecabet sodium showed a positive interaction with gastric mucin, as assessed by an increase in viscosity. Thus ecabet sodium may reduce the aggressive potential of gastric juice towards the mucosa, which may be relevant in the treatment of reflux oesophagitis and peptic ulcer disease. In addition, it may strengthen the mucus barrier in peptic ulcer disease and gastritis.     

Helicobacter pylori infection and GERD

Helicobacter pylori (H. pylori) is an important pathogen that is known to be associated with gastritis, peptic ulcer diseases, and gastric cancer. The association between H. pylori infection and gastro-esophageal reflux disease (GERD) is, however, uncertain. Recent studies indicate that the prevalence of H. pylori is significantly lower in patient with GERD from East Asia than in patients from Western Europe and North America, and that H. pylori might protect against GERD. The frequency of hypochlorhydria might due to atrophic gastritis induced by H. pylori infection is associated with the low prevalence of GERD in Japan.     

胆汁反流和幽门螺杆菌感染在胆汁反流性胃炎和消化性溃疡发病中的作用

目的探讨胆汁反流和幽门螺杆菌感染在胆汁反流性胃炎和消化性溃疡发病中的作用。方法采用病理组织学检查和快速尿素酶试验对76例胆汁反流性胃炎及22例兼有胆汁反流性胃炎和消化性溃疡的患者行幽门螺杆菌检测,并与29例消化性溃疡患者作对照。结果胆汁反流性胃炎组幽门螺杆菌阳性率为31.6%(24/76例),兼有胆汁反流性胃炎和消化性溃疡组幽门螺杆菌阳性率为59.0%(13/22例),消化性溃疡组幽门螺杆菌阳性率为72.4%(21/29例),前二组比较,差异有显著意义(P<0.05),后二组比较,差异无显著意义(P>0.05)。结论胆汁反流在胆汁反流性胃炎的发病中起主要作用,幽门螺杆菌感染在消化性溃疡的发病中起主要作用。胆汁反流和幽门螺杆菌感染在胆汁反流性胃炎和消化性溃疡的共同发病中互不明显影响,幽门螺杆菌感染所起的作用可能更大一些。     

Recent view of gastro-esophageal reflux disease according to the guideline for gastric ulcer treatment

The guideline for gastric ulcer treatment in Japan recommends eradication of Helicobacter pylori (H. pylori) for the first choice. Recently, it is well known that some patients develop gastro-esophageal reflux disease (GERD) after successful eradication. H. pylori infection may play a protective role against GERD by impairing gastric acid secretion. Acid secretion is influenced by the distribution of gastritis in the stomach. Antrum-predominant gastritis is associated with gastric hypersecretion. Patients with corpus-predominant gastritis have decreased acid secretion. The latter is common in Japan and at high risk of GERD after eradication. To arise GERD, both acid secretion and reflux of acid caused by hiatus hernia or gastro-esophageal dysmotility are needed. Although most of GERD developed after eradication are mild, severe GERD are also experienced at times. Recent view of GERD and H. pylori infection is described.     

Helicobacter pylori infection in gastric remnant cancer after gastrectomy

Patients who have undergone distal gastrectomy for peptic ulcer are at higher risk of developing gastric remnant cancer, and chronic bile reflux is believed to increase the risk of cancer in remnant stomach. In remnant stomach, carcinogenesis may be prevented by selecting the anastomosis method with a few reflux of intestinal juice including a bile acid. How Helicobacter pylori(H. pylori) infection participate in stomal gastritis and gastric remnant cancer, same as early gastric cancer in the intact stomach, is attended. H. pylori positive rate of remnant stomach is different by examination method and a report, but its rate is decreased every year after gastrectomy and in particular low in Billroth-II(B-II) anastomosis. B-II anastomosis is followed by a significantly lower rate than B-1. This may reflect the role of bile reflux because bile reflux interferes with colonization by H. pylori. Gastric cancer excision usual increase complicates gastric remnant stomach and H. pylori infection, but while H. pylori infection lasts after gastrectomy for gastric cancer, cell proliferation increase in remnant stomach. In remnant stomach after gastrectomy for gastric cancer, while H. pylori infection continues, H. pylori infection may cause remnant gastritis and a second cancer of remnant stomach. H. pylori infection and bile reflux seem to have a synergistic effect on cell proliferation in remnant stomach and may explain the increased risk of gastric remnant cancer. The cancer-causing dominant role might changed from H. pylori infection predominance to bile reflux every year after gastrectomy. Furthermore, a prophylactic effect to carcinogenesis by H. pylori eradication therapy is expected. Eradication of H. pylori after gastrectomy for gastric cancer has been recommended.     

Helicobacter pylori infection and eradication

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.