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.     

Duodenal ulcer treatment: progress from pH to HP

The treatment of duodenal ulcer has evolved from ineffective medical treatments through an era of surgical management, back to increasingly effective medical treatment. The advent of H2-receptor antagonists changed the outlook for ulcer patients. More recently, Helicobacter pylori , an organism which inhabits gastric mucosa exclusively, has been implicated in the pathogenesis of peptic ulcer. This bacterium is found in the stomachs of around 95% of duodenal ulcer patients. Its eradication is shown dramatically to improve the rate at which ulcers relapse. The mechanisms whereby it may cause ulceration are not established-we review current hypotheses. No method of eradication is 100% effective, and many different dual or triple therapy regimens have been tried. Metronidazole resistance is reported but its importance is not yet known. Helicobacter eradication is likely to prove a cost-effective and acceptable treatment for duodenal ulcer, and once its value has gained acceptance widespread uptake of this option is anticipated.     

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.     

Proton pump inhibitor for maintenance therapy of peptic ulcer]

The strategy for peptic ulcer therapy has been changing with the clinical application of the gastric proton pump inhibitor (PPI). In Japan, Miyoshi et al and Takemoto et al reported an earlier reepithelialization of peptic ulcer with omeprazole (OME) or lansoprazole (LAN) than famotidine (FAM). Miyoshi et al also reported that there was no significant difference between OME and FAM in ulcer relapse rate during a one year follow-up period. Therefore, there were two problems. One is application of PPI for prevention of ulcer relapse, and the other is the more accurate diagnosis of ulcer healing. Application of PPI for maintenance therapy is not yet realized in Japan, but, Lauritsen et al had already reported on the efficacy and safety of OME, 20 mg, three days a week and 10 mg, daily in prevention of duodenal ulcer relapse. Reepithelialization (red scar) is already established as a starting point of maintenance therapy, and from Miyake's report, a white scar is believed a favorable (non relapsing) end point.     

Proton pump inhibitors in the treatment of peptic ulcers resistant to H2-receptor antagonists]

The aim of this study is to evaluate the therapeutic effect of proton pump inhibitors on peptic ulcers resistant to H2-receptor antagonists. Patients with ulcers resistant to at least 3 months treatment with standard or greater doses of H2-receptor antagonists were treated with 20 mg of omeprazole or 30 mg of lansoprazole, once daily, for 2 to 8 weeks. Endoscopy was performed every 2 weeks to confirm ulcer healing. Eleven of 28 (39%) gastric ulcers healed within 4 weeks and 20 (71%) within 8 weeks with omeprazole. Eight of 19 (42%) gastric ulcers healed within 4 weeks and 14 (74%) within 8 weeks with lansoprazole. All of the duodenal ulcer healed within 6 weeks with omeprazole or lansoprazole. No adverse effects were observed in this study. These results suggest that proton pump inhibitors are highly effective in the treatment of peptic ulcer resistant to H2-receptor antagonists.     

Relapse of peptic ulcer after quick healing induced by proton pump inhibitors]

Peptic ulcers treated with a proton pump inhibitor heal more quickly than those treated with a histamine H2 receptor antagonist. Although satisfactory healing without relapse is desirable in the medical treatment of peptic ulcers, the relapse rate after treatment with proton pump inhibitors has not been sufficiently studied. Up to now, several reports have suggested that peptic ulcers treated with omeprazole recur less frequently than those treated with H2 antagonists. Our experimental studies on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers, gastric mucosal collagen synthesis etc., show that H2 antagonists have an inhibitory effect on wound healing, but that proton pump inhibitors do not. It is suggested, therefore, that proton pump inhibitors may at least have no undesirable effect on the natural history of peptic ulcer.     

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.     

Treatment of Helicobacter pylori infection

Helicobacter pylori infection has been shown to be the principal cause of peptic ulcer disease and has been associated with MALT lymphoma and gastric cancer. Eradication of H. pylori has been shown to change the natural history of peptic ulcer disease by preventing relapse and to reduce health care expenditures when compared with traditional therapy. Two-drug regimens have been superceded by three-drug regimens because they are more effective in eradication. Therapies with the highest efficacy are cost-effective because failed eradication is associated with high costs.     

雷贝拉唑与奥美拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡疗效比较--附40例分析

目的 :比较雷贝拉唑三联疗法与奥美拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡的疗效。方法 :将幽门螺杆菌阳性的消化性溃疡 85例分为两组 :治疗组 (雷贝拉唑三联疗法组 ) 4 0例 ,以雷贝拉唑 10mg、阿莫西林 10 0 0mg及甲硝唑 4 0 0mg每日 2次口服 ,治疗 1周后单独服用雷贝拉唑 10mg ,连服 7日 ;对照组 (奥美拉唑三联疗法组 ) 4 5例 :以奥美拉唑 10mg、阿莫西林 10 0 0mg及甲硝唑 4 0 0mg ,每日 2次口服 ,治疗 1周后单独服用奥美拉唑 10mg ,连服 7日。治疗期间每周门诊随诊 ,记录临床症状改善情况 ,用药结束 1个月后复查胃镜并检测幽门螺杆菌结果。结果 :治疗组和对照组治疗 1日的临床症状缓解率分别为 83%、 6 2 % ,差异有统计学意义 (P <0 0 5 ) ;1周后的症状缓解率均为 98%。治疗组和对照组的溃疡愈合率分别为 93%和 76 % ,差异有统计学意义 (P <0 0 5 ) ;治疗组和对照组的总有效率分别为 98%和 96 % ,差异无统计学意义 (P >0 0 5 )。治疗组和对照组的幽门螺杆菌根除率分别为 88%和 78% ,差异无统计学意义 (P >0 0 5 )。结论 :两组方案均能有效治疗消化性溃疡和缓解临床症状 ,并能有效地根除幽门螺杆菌。但雷贝拉唑三联疗法在快速改善临床症状和促进溃疡愈合方面优于奥美拉唑三联疗法。     

H2-receptor antagonist-refractory ulcer--its pathophysiology and role of proton-pump inhibitors]

Among H2-receptor antagonist (H2RA)-refractory ulcers, non-responders that did not heal after 5 months therapy had high intraluminal pH in the basal condition and high sensitivity to inhibition of acid secretion by H2RA but possessed gastric mucosa to generate less prostaglandins. Combination therapy of PGE1-analogue with H2RA healed these ulcers by 60%. Proton-pump inhibitor (PPI) exerted a complete inhibition of acid secretion in these patients and the rate of healing was 88%. Helicobacter pylori was present in the mucosa of all 4 ulcer patients refractory to treatment with PPI. The ulcers healed in 3 out of 4 patients after eradication of H. pylori. It is suggested that PG supplement or complete inhibition of acid secretion is effective for ulcers in H2RA-non-responders. PPI-refractory ulcers may relate to H. pylori infection.     

雷贝拉唑与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡疗效比较

目的:比较雷贝拉唑三联疗法与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡的疗效。方法:将幽门螺杆菌阳性的消化性溃疡83例分为两组:治疗组(雷贝拉唑三联疗法组)41例,以雷贝拉唑10mg,阿莫西林1000mg及甲硝唑400mg每日2次口服,治疗1周后单独服用雷贝拉唑10mg,连服7d;对照组(兰索拉唑三联疗法组)42例:以兰索拉唑30mg,阿莫西林1000mg及甲硝唑400mg,每日2次口服,治疗1周后单独服用兰索拉唑30mg,连服7d。治疗期间每周门诊随诊,记录临床症状改善情况,用药结束1个月后复查胃镜并检测幽门螺杆菌结果。结果:治疗组和对照组1d的临床症状缓解率分别为80%、60%,差异有统计学意义(P<0.05);1周后症状缓解率均为98%。治疗组和对照组的溃疡愈合率分别为93%和76%,差异有统计学意义(P<0.05);治疗组和对照组的总有效率分别为98%和96%,差异无统计学意义(P>0.05)。治疗组和对照组的幽门螺杆菌根除率分别85%和81%,差异无统计学意义(P>0.05)。结论:两组方案均能有效治疗消化性溃疡和缓解临床症状,并能有效地根除幽门螺杆菌。但雷贝拉唑三联疗法在改善临床症状和促进溃疡愈合方面优于兰索拉唑三联疗法。     

Influence of H. pylori infection on upper gastrointestinal damage

H. pylori infection and low-dose aspirin (LDA) are not only independent causal factors of peptic ulcer and gastrointestinal bleeding, they also have synergistic and additive effects. H. pylori infection rate has drastically decreased over the past decade to 34.3% amongst people in their 40's, 28.0% amongst those in their 30's, and 15.7% amongst those in their 20's. Therefore, LDA are expected to become more important factor of peptic ulcer in the near future. The incidence of peptic ulcer induced by LDA was 15.8% (16/101) in authors' hospital. Deep ulcers(more than proper muscularis layer) were only 4 cases, shallow ulcers(submucosal layer) were 12 cases. All deep ulcers were gastric ulcers (3 H. pylori positive, 1 negative), on the other hand shallow ulcers were 8 gastric ulcers (3 H. pylori positive, 5 negative), and 4 duodenal ulcers (1 H. pylori positive, 3 negative). Majority of peptic ulcers induced by LDA were shallow, and independent on H. pylori infection.     

Effects of Helicobacter pylori eradication therapy on the healing process of peptic ulcers

The advent of H2-receptor antagonists (H2RA) and proton pump inhibitors (PPI) has particularly revolutionized the treatment of peptic ulcer disease. Most cases can now be successfully controlled by medical treatment with H2RA and PPI, but a high rate of ulcer recurrence remains an important problem. The quality of ulcer healing (QOUH) has therefore received increasing attention, and various investigators have attempted to define the conditions required for nonrecurrence. Ulcer scars with a good QOUH are considered to have a very low risk of recurrence. Recent studies have confirmed that recurrence of peptic ulcer can be suppressed markedly by eradication of Helicobacter pylori (H. p). Moreover, various types of endoscopic examinations (conventional observation, dye-contrast endoscopy, magnifying endoscopy, endoscopic ultrasonography, pharmacoendoscopy) have confirmed that the QOUH after eradication of H. p is better than that after conventional anti-ulcer therapy. H. p eradication therapy may become treatment of first choice for peptic ulcers.     

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.     

Recurrent peptic ulcer after gastric surgery]

Recurrent peptic ulcer after gastric surgery differs from duodenal ulcer in that they usually occur with low acid output, which is sufficient to cause ulceration in predisposed stomach or anastomosis. The proton pump inhibitor (PPI), significantly more potent and long-acting than H2-blocker, is expected to be more effective for postoperative recurrent ulcers. We evaluated the efficacy of omeprazole (OPZ) on recurrent ulcers in 12 patients following either gastrectomy or vagotomy. The healing rate after 4 week treatment with OPZ was 58% and increased to 100% after 8 week. Evaluation of quick symptom relief also supported the efficacy of OPZ treatment. These findings showed that OPZ treatment resulted in a more rapid healing of recurrent ulcers compared with H2-blocker. It remains to be clarified whether quit of treatment with PPI would induce high ulcer relapse rates, and whether maintenance therapy with PPI would be the only alternative therapy for surgical intervention.     

The effectiveness of 7-day combined Helicobacter eradication therapy in patients with peptic ulcer and chronic gastritis

Epidemiological and clinical findings suggest that the spread of Helicobacter pylori (H.p.) infection as an etiological and pathogenetic agent is of prime importance for patients with pelvic ulcer and chronic gastritis. However, there are relatively scanty papers on the impact of therapy against H.p. on its eradication rate, symptom arrest, and the course of diseases. A great deal of drug combinations have been proposed to eradicate H.p. infection and some of them are even classical (omeprazole in combination with 2-3 antibiotics). The H.p. eradication with this combination for 7 days is as high as 85-90%. These regimens are recommended for practical application in Europe and Russia. The authors' studies in 90 patients (34 with duodenal ulcers, 34 with gastric ulcers, and 28 with chronic duodenitis) indicate that lansofed used in 7-day combined therapy is highly effective in suppressing acid production, abolishing symptoms during an exacerbation of peptic ulcer (gastroduodenitis) and in eradicating H.p. infection. There is evidence for that the use of the agent in combination with 2 and 3 anti-H.p. drugs rapidly arrest the symptoms of a disease, frequently diminishes an inflammatory process and lead to a remission.     

Endoscopic ultrasonographic study of gastric ulcer treated with proton pump inhibitor]

We examined 70 cases of gastric ulcer by endoscopic ultrasonography. Of these, 18 cases were treated with proton pump inhibitor (PPI), another cases were treated with histamine H2 receptor antagonist or mucosal protective drugs. The Endoscopic cumulative healing rate at the eighth week was 71.4% in all gastric ulcers. On the other hand, all of gastric ulcers treated with PPI were healed within eight weeks endoscopically. Gastric ulcers which were revealed ultrasonographically to be refractory with were healed by PPI therapy. The length of the ulcer echo in gastric ulcers treated with PPI was shorter than that in gastric ulcer treated by other drugs. In spite of endoscopic scar findings, a wide ulcer echo was observed in some cases.     

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.     

Peptic ulcer recurrence after successful eradication of Helicobacter pylori--clinical characteristics and management

Peptic ulcer recurrence after successful eradication of Helicobacter pylori(H. pylori) is not rare. We evaluated the effect of H. pylori eradication on prevention of gastric ulcer recurrence. Ulcer recurrence had occurred in 20 of 256 H. pylori-eradicated patients, and most of ulcer recurrence were found within 1 year after eradication. NSAIDs and psychological stress, but not sex, smoking habit, drinking habit, and past history of ulcer, seem to be associated with ulcer recurrence. Intractable ulcers after the eradication of H. pylori frequently recurred. Some recurrent ulcers were refractory to treatment with H2-receptor antagonists or proton pump inhibitors. The mechanism(s) by which healed ulcers recur after successful eradication of H. pylori remains unclear.