Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or low (n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful (n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection.     

Tailor-made medicine in Helicobacter pylori eradication therapy

Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype. CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians. However, we should be aware that the increase of antimicrobial-resistant strains of H. pylori may force us to examine antimicrobial susceptibility of all patients in order to achieve a more than 80% eradication rate at first-line therapy in the near future. We should also have proper knowledge of the influence of the CYP2C19 genetic polymorphism on treatment efficacy according to the variety of PPI and the combination with other drugs.     

幽门螺杆菌根除与消化性溃疡复发的关系

目的　研究根除幽门螺杆菌(HP)与消化性溃疡(PU)复发的关系。方法　对HP根除组与HP未根除组随访3年,比较PU复发率。结果　HP根除组与HP未根除组溃疡复发率差异显著(P <0 .0 5 )。结论　根除HP可明显降低PU的复发。     

Anti-ulcer therapy after eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) infection is the cause of the frequent relapse of peptic ulcer disease. Successful eradication therapy of H. pylori is associated with a decline in the recurrence of peptic ulcer. In this paper, we discussed the significance of anti-ulcer therapy after H. pylori eradication therapy. In patients with duodenal ulcer, maintenance therapy for preventing ulcer recurrence is not necessary because the rate of ulcer recurrence after eradication therapy is very low. However, in patients with gastric ulcer, the rate of ulcer relapse and reflux esophagitis ranges between 5-10% in the Japanese population even after successful eradication therapy; therefore, maintenance therapy for 1 year may be permissible in patients with gastric ulcer even after successful eradication therapy.     

Side effects of Helicobacter pylori eradication therapy

The authors found that antihelicobacter therapy is accompanied by various side-effects, such as allergic reactions, gastrointestinal disturbances, dysbacteriosis, hematological disorders, and sometimes toxic hepatic lesions, depending on what antibiotic and in what doses is applied, as well as on the duration of antibiotic therapy.     

左克胶囊三联疗法根除幽门螺杆菌感染

目的观察左氧氟沙星短程三联疗法根除幽门螺杆菌（Hp）感染的疗效。方法100例Hp阳性患者[A组，男62例，女38例；年龄（59±11）岁；十二指肠球部溃疡（DU）62例，胃溃疡（GU）38例]给予泮托拉唑40mg，po，bid，左氧氟沙星200mg及阿莫西林1000mg，po，bid。另102例Hp阳性患者[B组，男59例，女43例；年龄（57±9）岁；DU58例，GU44例]给予泮托拉唑40mg，克拉霉素500mg及阿莫西林1000mg，po，bid。疗程均为1周。疗程结束后4～6周复查胃镜及Hp。结果A、B两组抗Hp治疗结束后4—6周停用PPI2周后，Hp根除率各为87％、79％（P〉0．05），均无严重不良反应。结论Hp耐药菌株多见，左旋氧氟沙星联合奥美拉唑和阿莫西林是一种安全、疗效高、耐受性好的治疗Hp感染的方案。     

Effects of Helicobacter pylori(Hp) eradication on gastric mucosal pathophysiology in Hp-positive, NSAIDs-induced gastric ulcer

It has been suggested that the mechanisms of NSAIDs-induced peptic ulcer disease are totally different from those induced by Hp. Although a number of studies have examined the effects of Hp eradication on pathophysiology of NSAIDs-induced ulcer diseases, the results have been controversial. At present, therefore, we do not know whether Hp should be eradicated in Hp-positive NSAIDs-induced ulcer patients. Recent studies have shown that both Hp eradication and NSAIDs treatment increases gastric acid secretion, and often causes mucosal lesions in upper GI tract. Based on this back ground, we have decided to review pathophysiology of the Hp-dependent ulcer, and the NSAIDs-induced ulcer. We also discussed the merit and demerit of Hp eradication on gastric mucosal pathophysiology in Hp-positive, NSAIDs-induced ulcer.     

Long-term outcomes of gastric mucosa-associated lymphoid tissue lymphomas after Helicobacter pylori eradication therapy

Mucosa-associated lymphoid tissue (MALT) lymphomas are localized primarily in the gastrointestinal tract and are characterized by an indolent nature and favorable outcome with specific therapy. Gastric MALT lymphomas are closely linked to Helicobacter pylori (H. pylori) infection, for which eradication therapy is recognized as an effective primary treatment for the disease. However, there is little information about long-term outcomes after the therapy. In the present study, we elucidated the long-term outcomes of 74 patients (70 H. pylori-positive and 4 negative cases) followed up by endoscopy at least 12 months after exclusive eradication therapy alone. The median follow-up period was 46 months. When the remission status was estimated at the time point of 12 months post-eradication, the numbers of patients with complete remission (CR), histologically residual disease with macroscopic normalization (hRD), partial remission with more than 50% tumor reduction (PR) or no response (NR) were 56, 12, 2 and 4, respectively. During follow-ups of over 12 months post-eradication, 11 of the 12 hRD cases were belatedly induced to CR but one CR case histologically relapsed into hRD. One of the 2 PR cases eventually turned into hRD 20 months later. Therefore, 66 CR, 3 hRD, 1 PR, and 4 NR cases (including 3 H. pylori-negative) were identified at the last follow-up of the present study. All 74 patients were followed up without any second-line therapies, but none exhibited disease progression. Thus, the long-term outcome of localized gastric MALT lymphoma after H. pylori eradication therapy was favorable. A watch and wait strategy may be a reasonable approach for hRD since the majority might be in the process of turning into delayed CR.     

Helicobacter pylori eradication and associated changes in the gastric mucosa

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.     

Helicobacter pylori eradication and associated changes in the gastric mucosa

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.     

Gastric ulcer and Helicobacter pylori in the elderly population

Recently, the incidence of gastric ulcer in Japanese elderly people has been increasing and the number of deaths associated with gastric ulcer has not decreased. Helicobacter pylori infection rates in elderly patients with gastric ulcer are lower than those in non-elderly patients. NSAIDs including aspirin and many other factors influence the development of gastric ulcer. Gastric ulcers occur in the upper part of the stomach and often bleed. In addition, elderly patients tend to have no abdominal symptoms other than bleeding. According to guidelines, endoscopic hemostasis is performed in cases with active bleeding. Eradication therapy is recommended for elderly patients as for as non-elderly patients, and antacids are administered to patients who are negative for H. pylori or have a relapse of ulcers.     

Significance of H. pylori eradication in treatment and prevention for low-dose aspirin induced gastric ulcer of elderly

Although treatment and prevention for low-dose aspirin (LDA) induced gastrointestinal mucosal injury is important problem, significance of H. pylori eradication has not been clarified. NSAIDs including LDA and H. pylori infection are independent causal factors for gastroduodenal ulcer. However, the interaction between these factors is complicated. H. pylori eradication can reduce the risk of NSAIDs induced ulcer in NSAIDs naive patients. However, H. pylori eradication is not recommended in NSAIDs user because of no ulcer suppression and ulcer healing delay. In prevention of LDA induced ulcer recurrence, H. pylori eradication plus PPI treatment are necessary.     

Effect of the eradication of Helicobacter pylori on peptic ulcer healing

Acid suppressive therapy with H2 receptor antagonist or proton pump inhibitor can hardly shift peptic ulcers to S2 stage (white scar). As a result, judgement of ulcer healing has been made at S1 stage (red scar). However, it has been a problem that many ulcer scars relapse. Helicobacter pylori eradication therapy can prevent peptic ulcers from relapsing. The eradication therapy shifted 92% gastric ulcers from all stages to S2 stage after 24 months. We has divided S1 stage categorized by conventional endoscopy into H3-C stage (with small defect of mucosa) and S1-C stage by dye contrast method. The ulcers at H3-C stage relapse more frequently than those at S1-C stage. The acid suppressive therapy shifted only 7%, 15% gastric ulcers at H3-C stage, S1-C stage to S2-C stage after 6 months, respectedly. On the other hand, the eradication therapy shifted 56%, 65% gastric ulcers at H3-C stage, S1-C stage to S2-C stage, respectedly. It may be one reason why the eradication therapy prevents peptic ulcers from relapsing that the therapy shifts almost peptic ulcers to S2 stage.     

The effect of Helicobacter pylori eradication on duodenal gastric metaplasia

We investigated the incidence of duodenal gastric metaplasia and its response to Helicobacter pylori eradication in patients with duodenal ulcer or erosive duodenitis. Gastric and duodenal biopsies were taken from patients with endoscopically detected H. pylori positive duodenal ulcer or erosive duodenitis, and the presence and extent of duodenal gastric metaplasia was recorded. Patients were given omeprazole 20 mg twice daily for 2 weeks, and amoxicillin 1 g and clarithromycin 500 mg twice daily for 10 days, and then ranitidine for a further 8 weeks. Biopsies were repeated 6 months after the start of treatment. Duodenal gastric metaplasia was initially present in 22 patients (52%) and was more frequent in ulcer patients than in duodenitis patients, but not significantly so (69% versus 45%). After treatment, H. pylori was eradicated in 68% of duodenal gastric metaplasia patients and the duodenum was normal endoscopically in 85% of these patients. Duodenal gastric metaplasia was improved or eliminated in 12/15 H. pylori eradicators (80%) and in 5/7 H. pylori non-eradicators (71%), a non-significant difference. The improvement in duodenal gastric metaplasia appeared to be independent of H. pylori eradication.     

幽门螺杆菌根除后胃黏膜的病理变迁

目的探讨根除幽门螺杆菌(Hp)对胃黏膜萎缩、肠上皮化生等癌前病变的转归,以及胃黏膜上皮细胞增殖指标ki-67表达的影响。方法67例Hp感染且有胃黏膜萎缩和(或)肠上皮化生的慢性胃炎患者,随机分为实验组(37例)和对照组(30例),分别给予Hp根除和对症治疗,1年后复查,比较Hp根除与否对胃黏膜萎缩、肠上皮化生等癌前病变的影响;用免疫组化方法检测治疗前后胃黏膜上皮细胞增殖指标ki-67的表达,比较Hp根除与否对它的影响。结果实验组炎症程度减轻(34/37,91.9%,P<0.01),活动性炎症者减少(P<0.01),萎缩、肠上皮化生等癌前病变减轻或逆转(21/32,65.6%vs15/26,57.7%,均P<0.05);ki-67表达降低(46.5±27.7vs15.4±18.7,P<0.01)。结论根除Hp可使胃黏膜炎症程度减轻,活动性炎症消失,萎缩、肠化等癌前病变减轻或逆转,胃黏膜上皮细胞增殖指标ki-67表达减少,从而有利于预防胃癌的发生。