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.     

Current state and measures of NSAIDs induced ulcer

In recent years, the incidence of Helicobacter pylori (H. pylori) infection has been decreasing and the incidence of peptic ulcer and bleeding ulcer induced by NSAIDs, especially low-dose aspirin (LDA), have been increasing. PPI and PG are useful for treatment and prevention of ulcers in patients receiving continuous administration of NSAIDs and/or LDA. H. pylori eradication is effective if performed before the start of NSAIDs administration, but a beneficial effect of H. pylori eradication performed during NSAIDs treatment cannot be expected. The incidence of ulcers is lower when administering COX-2-selective inhibitor than when administering non-selective NSAIDs, but attention must be given to cardiovascular events as side effects when administering COX-2-selective inhibitor.     

Selection of antibiotics and planning of eradication for H. pylori infection

There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori.     

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.     

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.     

Proton pump inhibitor H2 receptor antagonist

Recently, Japanese guidelines for the treatment and prevention of peptic ulcers were established by the Japanese Society of Gastroenterology. Herein, we focus on proton pump inhibitor(PPI) and H2 receptor antagonist (H2RA) for prophylaxis and treatment of peptic ulcer associated with NSAIDs including low dose of aspirin. Double dose of H2RAs are effective at preventing chronic NSAID related ulcers, however, the effect is not superior to PPI. Full-dose misoprostol and PPI are clinically equivalent, although the potential adverse effects of misoprostol are a major cause of poor compliance. Overall, PPIs have the best profile of efficacy and side-effects for the healing and prevention of NSAID-associated ulcers, especially in the patients with high risk, such as history of peptic ulcer.     

Several points that should be noticed during PPI treatment for peptic ulcers in elderly patients

Proton pump inhibitor(PPI) is used for the treatment of peptic ulcer diseases for the following three purposes. Firstly, it is used to facilitate the ulcer healing and pain relief. Secondly, it is used for the eradication of H. pylori to minimize the recurrence of ulcer diseases. Thirdly, intravenous infusion of PPI is used for the hemostasis in patients with bleeding ulcers. Plasma concentration and acid suppressing effect of PPI are reported to be slightly augmented when standard doses of PPI are used in elderly cases. Since PPI is a safe drug and age-related increase in its plasma concentration is not remarkable, the dose adjustment of PPI may not be necessary even in elderly patients. Some PPIs are, however, reported to have metabolic interactions with other drugs such as diazepam and digoxin. Therefore drug interaction should be considered when the PPI is administered to the elderly with accompanying diseases.     

Trends in peptic ulcer pharmacotherapy

Considering the diseases of the stomach and duodenum, peptic ulcer has been the one with a significant clinical impact. The pathophysiology of peptic ulcer has centred on an imbalance between aggressive and protective factors. The discovery of Helicobacter pylori as a cause of peptic ulcer has changed our approach greatly towards this disease. Despite the decreasing frequency of H. pylori-induced peptic ulcers, peptic ulcer remains a major clinical problem partly because nonsteroidal anti-inflammatory drug (NSAID)-related ulcers and hospital admissions for ulcer complications associated with NSAIDs have increased in frequency. The interaction between H. pylori and NSAIDs is one of the most controversial issues in peptic ulcer. In this article, current concepts of peptic ulcer etiopathogenesis and the management of peptic ulcer according to the etiology were reviewed.     

Ulcers and gastritis

This article reviews recently published literature regarding ulcers and gastritis. Although endoscopy is the most useful procedure for diagnosis in the upper gastrointestinal tract, complications do occur, and procedure-related costs are significant. The appropriate indication for endoscopy has recently been debated. Helicobacter pylori is known to be an important pathogen involved in gastric and duodenal inflammation. Peptic ulcer disease and severe gastric mucosal injury are caused by virulent strains, and many reports have focused on CagA. Follow-up studies on surveillance endoscopy in patients with peptic ulcer or gastritis report that patients with atrophic gastritis and intestinal metaplasia are at significantly higher risk for gastric cancer. H. pylori eradication sometimes causes gastroduodenal erosion and reflux esophagitis, and the mechanisms involved have been revealed. Proton-pump inhibitors are useful in the treatment of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs), reflux esophagitis, and for preventing rebleeding after endoscopic hemostasis, but the effect of long-term acid suppression on the gastric mucosa is still a matter of debate. H. pylori infection and NSAID intake are both risk factors for peptic ulcer disease, and are important aspects in this field.     

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.     

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.     

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.     

Guidelines for the management of Helicobacter pylori--Maastricht III-2005 and Japanese guidelines

The guidelines on the management of Helicobacter pylori were updated at the European Helicobacter study group third Maastricht consensus conference in March 2005. Especially, this conference emphasis on the management of non ulcer dyspepsia, GERD, and the patients who use non steroidal anti-inflammatory drug. Eradication of H. pylori is recommended in patients with peptic ulcer, low grade MALT lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura and first degree relatives of patients with gastric cancer. H. pylori eradication is less effective than proton pomp inhibitor(PPI) treatment in preventing ulcer recurrence in long term NSAIDs users. This meeting also emphasized on the relationship between H. pylori and gastric cancer. The guideline concluded that H. pylori eradication has the potential to reduce the risk of gastric cancer development. Japanese guideline in 2003 does not mention the effect of eradication for prevention of gastric cancer. The H. pylori eradication and new strategy should be desirable for global strategy of gastric cancer prevention.     

Pathologic characteristics of gastric ulcer in the aged

The use of aspirin continues to increase as a result of accumulation of evidence of benefits in treatment strategies for cardiovascular disease. These antiplatelet agents, however, have recognizable risks of gastrointestinal complications such as ulceration and related bleeding. Based on the published guidelines in Japan, the cause of gastric ulcer is divided roughly into Helicobacter pylori infection and nonsteroidal antiinflammatory drug (NSAID) including aspirin. With the decrease of H. pylori infection rate in a young and that of ulcer recurrence by H. pylori eradication therapy, the cases with peptic ulcer that is come from H. pylori infection have decreased in Japan. On the other hand, gastric ulcer based on the use of aspirin and NSAID have increased. The author reviewed pathologic characteristics of gastric ulcer in the aged in this report.     

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.     

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。     

Evaluation of the efficacy and the cost-effectiveness of proton pump inhibitor-based dual and triple therapy regimens for H. pylori eradication in peptic ulcer disease

To evaluate the efficacy and the cost-effectiveness of H. pylori eradication for the treatment of peptic ulcer disease, a randomized controlled trial to compare the efficacy of proton pump inhibitor-based dual and triple regimens was conducted. A decision analysis was also performed to assess H. pylori eradication compared to the conventional maintenance strategy. Two hundred and thirty-four peptic ulcer patients suffering from H. pylori infection were randomly treated with either omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) or with omeprazole 20 mg bid + clarithromycin 400 mg bid (OC) for 14 days. The eradication rate with OAC was 87.6% (92/105) (95% Confidence Interval (CI): 81-94%), which was significantly higher than that with OC (61.9% (60/97) (95% CI: 52-72%)) (p < 0.001, chi 2 test). Both regimens were safe and well tolerated. H. pylori eradication was more effective and less costly than conventional strategy in a long term perspective. OAC was more cost-effective than OC. In conclusion, H. pylori eradication is a cost-effective alternative to conventional treatment. We recommend 2 weeks triple regimen with omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) as a first-line treatment in all patients with peptic ulcers associated with H. pylori infection.     

A randomized comparison of triple therapy Helicobacter pylori eradication regimens in children with peptic ulcers

An open, randomized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease. A total of 106 children (5 - 15 years) were treated for 1 week with metronidazole, 30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age; generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily. The H. pylori eradication rate was significantly higher in patients receiving proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%) or ranitidine (74.3%), and this was associated with a trend towards faster ulcer healing. It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H. pylori and ulcer healing in children with peptic ulcer disease, and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this study.     

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。