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.     

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.     

PPI treatment for gastric ulcer patients in the elderly

Proton pump inhibitor (PPI) is an effective and safe medication for the elderly people for the treatment of peptic ulcer disease. However, some PPIs have been reported that they have metabolic interactions with some drugs. Therefore, drug-interactions should be considered when the PPI is prescribed to the elderly people. The number of NSAIDs ulcer patients is thought to increase along with the increase of those who take NSAIDs in the elderly. Although PPI is indispensable for the prevention of the NSAIDs ulcer, PPI has not obtained authorization for the purpose of prevention in Japan. PPIs are strongly expected to be approved for prevention of NSAIDs ulcer by the Japanese government in the near future.     

Evaluation of the efficacy and the cost-effectiveness of maintenance treatment of gastroesophageal reflux disease: proton pump inhibitor versus histamine-2-receptor antagonist

GERD is a common condition and acid-suppressing agents are the mainstay of treatment. A cost-effectiveness analysis comparing a PPI, lansoprazole (LPZ) and a H2RA, famotidine (FAM) for the maintenance treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The time period studied was 6 months and payer perspective was chosen. Transition probabilities were estimated from meta-analyses. Expected days without esophagitis (healthy days) were 166 for LPZ 30 mg/day, 161 for LPZ 15 mg/day and 143 for FAM 40 mg/day. Direct costs were 55,624 yen for LPZ 30 mg/day, 42,078 yen for LPZ 15 mg/day and 67,969 yen for FAM 40 mg/day. Cost-effectiveness ratio (direct costs/healthy days) was 335 yen for LPZ 30 mg/day, 262 yen for LPZ 15 mg/day and 477 yen for FAM 40 mg/day. Lansoprazole was superior to famotidine with regard to both efficacy and cost-effectiveness and therefore is the preferred therapeutic agent for the maintenance treatment of GERD.     

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.     

Long-term management of peptic ulcer disease

Maintenance therapy to reduce the risk of ulcer relapse and subsequent ulcer complications should be offered to patients who are likely to suffer a relapse by virtue of their past history or current risk factors. The most effective form of ulcer maintenance therapy appears to be continuous low-dose nocturnal therapy with H2-receptor antagonists. Patients who are observed expectantly and develop recurrent ulcer symptoms can be treated with full-strength therapy on an intermittent basis. Patients with a definite seasonal trend to their ulcer disease may benefit from a seasonal approach to therapy. Ulcer surgery is reserved for patients with ulcer complications or severe symptoms unresponsive to standard maintenance therapy. Just how long continuous low-dose maintenance therapy can or should be continued remains unclear. Whether ulcer disease is ever truly cured (never to recur again), as suggested by pre-endoscopic studies, is a matter of conjecture. Nevertheless, the use of maintenance-dose therapy appears to be safe over relatively long periods of time, and it appears that cumulative ulcer relapse rates decline with continued use of such therapy. The risk of recurrent symptoms, hemorrhage, and other complications is also reduced by maintenance therapy, and the economic aspects of ulcer disease are influenced in a positive fashion by these regimens. The role that C. pylori will ultimately play in the etiology and pathogenesis of peptic ulcers and their relapse is still not known with any certainty, although it appears to represent an important marker (if not an important pathogenetic cause) for ulcer disease. As such, it may be considered a risk factor to be eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials

BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.     

胸腺蛋白治疗消化性溃疡出血的疗效观察

目的观察胸腺蛋白对消化性溃疡出血的治疗及预防复发作用。方法将185例消化性溃疡合并上消化道出血的患者随机分为单纯奥美拉叹组和奥美拉唑＋胸腺蛋白组,每组分别为91例和94例。统计分析两组消化性溃疡出血的平均止血时间、治疗有效率及随访1年的出血复发率。结果奥美拉唑＋胸腺蛋白组与单纯奥美拉唑组比较,胃溃疡出血的平均止血时间下降有非常显著差异（P＜0．01）;而十二指肠球部溃疡出血的平均止血时间下降有显著差异（P＜0．05）。治疗胃溃疡出血、十二指肠球部溃疡出血的有效率无显著差异（P＜0．05）;但胃溃疡出血及十二指肠球部溃疡出血1年复发率下降分别有显著差异（P＜0．05）和非常显著差异（P＜0．01）。结论胸腺蛋白有缩短消化性溃疡出血的止血时间及预防出血复发作用。     

Eradication of Helicobacter pylori in Japan]

Twenty five years has passed since the re-discovery of Helicobacter pylori. Many people have studied on this organism since that time. Some mechanisms about gastric mucosal inflammation have been clarified, and pathogenesis of peptic ulcer formation and gastric cancer have been solved. H. pylori infection is related to chronic gastritis, peptic ulcer, gastric carcinoma, and MALToma. In 1998, it was reported that gastric cancer occurred in H. pylori infected mongolian gerbils. In Japan, the prevalence of peptic ulcer and gastric cancer is very high. Therefore, the treatment for H. pylori infection is necessary to prevent occurrence of these diseases. To treat H. pylori infection, various regimen have been tried. Triple therapy with PPI and two antibiotics is recommended for cure of H. pylori infection in European and US guidelines. Some guidelines for management of H. pylori infection and regimen were shown in this part.     

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.     

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.     

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.     

Peptic ulcer in patients with diabetes mellitus

It is well recognized that diabetes mellitus develop a variety of complications during the course of disease, such as diabetic triopathy. After one to two decades of overt disease, approximately 30-60% of diabetics develop clinical signs of visceral autonomic neuropathy. Peptic ulcer patients with diabetes mellitus have these complicated backgrounds. The prevalence of peptic ulcer disease in asymptomatic diabetic patients was reported as 5.3% to 7.3% in Japan. We evaluated the efficacy of Helicobacter pylori eradication therapy in peptic ulcer patients with non-insulin dependent diabetes mellitus. The cure rate of peptic ulcer and gastritis score at 8 weeks after eradication therapy is similar with non-diabetic patients. Our data suggests that the eradication of Helicobacter pylori becomes a first therapy in peptic ulcer patients with non-insulin dependent diabetes mellitus.     

Suitable diagnostic methods for H. pylori infection after eradication therapy

Urease test, histology, culture, urea breath test(UBT) and stool antigen test are accurate tests for Helicobacter pylori diagnosis. General practitioners are now going to test peptic ulcer disease patients with these tests before and after in Japan. To test with high accuracy after eradication therapy, it is important that examination should be done over 4 weeks after cessation of treatment with PPI and antibiotics. UBT and stool antigen test are suitable tests for diagnosis of Helicobacter pylori infection after treatment.     

Maintenance therapy of mild form of GERD by H2 receptor antagonists

Because of high relapse rate after the healing by proton pump inhibitor(PPI) or H2 receptor antagonist(H2RA), GERD usually needs long time maintenance therapy. PPI is superior to H2RA in the first line as well as maintenance therapy. PPI is necessary for severe cases of GERD. However, H2RA is sufficient for milder form of GERD patients. Among the H2RA using in Japan, nizatidine has known to stimulate gastric emptying and elevate LES pressure. Nizatidine may be superior to other H2RAs in the treatment of GERD. Recently, nocturnal acid breakthrough which night time acid is secreted even PPI is administered twice daily has been documented. H2RAs are stronger than PPI to inhibit nocturnal acid breakthrough and may be better than night time acid reflux.     

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.     

Cost-effectiveness of proton pump inhibitor therapy for acute peptic ulcer-related bleeding

OBJECTIVE: The purpose of this investigation was to perform a cost-effectiveness analysis of adjunctive oral and intravenous proton pump inhibitor (PPI) therapies for patients with acute peptic ulcer-related bleeding of sufficient severity to warrant hospitalization. DESIGN: Cost-effectiveness investigation. Four clinical scenarios were considered: scenario 1, diagnostic endoscopy with oral PPI therapy; scenario 2, diagnostic and therapeutic endoscopy with high-dose intravenous PPI therapy; scenario 3, diagnostic and therapeutic endoscopy available with oral PPI therapy; and scenario 4, diagnostic and therapeutic endoscopy (no PPI). Effectiveness was evaluated in terms of episodes of bleeding averted and quality-adjusted life years. SETTING: University teaching hospital in the United States. PATIENTS: Hospitalized patients with acute peptic ulcer bleeding. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Therapeutic endoscopy with high-dose intravenous PPI therapy (scenario 2) was the most cost-effective approach in terms of bleeding episode averted (8,490 vs. 10,201 US dollars for scenario 1, 8,756 US dollars for scenario 3, and 12,459 US dollars for scenario 4) and per quality-adjusted life year (4,810 vs. 5,533 US dollars for scenario 1, 4,946 US dollars for scenario 3, and 5,876 US dollars for scenario 4). The high-dose intravenous PPI scenario was the dominant approach as evidenced by both superior effectiveness and lower costs over the range of probability and cost variables used in the sensitivity analysis. However, the dominance would be lost if the purchase cost of the intravenous PPI was substantially higher than the baseline cost assumed in this investigation (61 US dollars per 3-day course of therapy). CONCLUSION: High-dose intravenous PPI therapy in conjunction with therapeutic endoscopy is the most cost-effective approach for the management of hospitalized patients with acute peptic ulcer bleeding.     

The present status and problems of Helicobacter pylori eradication therapy with a special reference to gastric cancer

Since the eradication therapy of Helicobacter pylori(H. pylori) for peptic ulcer was covered by Japanese health insurance at 2000 November, this therapy has been generalized in Japan. However, some problems have cropped up at the time, for example, emergence of clarithromycin resistant bacterium etc. On the other hand, investigation of relation between H. pylori and gastric cancer is making progress. Uemura, et al. demonstrated H. pylori had an important role for gastric carcinogenesis by the elegant prospective study in 2001. Under the present circumstances, the Japanese society of Helicobacter Research has to reconsider the guideline for eradication therapy. In this paper, we would like to state the present status and problems of eradication therapy of the current guideline for eradication therapy, especially focusing on gastric cancer.     

长期使用质子泵抑制剂对肠道菌群的影响

目的观察胃食管反流病和消化性溃疡患者长期使用质子泵抑制剂治疗后肠道菌群变化。方法选取胃食管反流病及消化性溃疡患者60例（观察组）,口服奥美拉唑,20mg,每日2次,疗程8周;选取健康志愿者20例（对照组）;利用实时荧光定量聚合酶链反应（PCR）检测观察组患者服药前、服药后4周、8周及对照组健康者清晨粪便中大肠杆菌、肠球菌属、双歧杆菌属及乳酸杆菌属数量,并对各目标菌群数量进行比较分析。结果与对照组相比,观察组患者服药前及服药后4周粪便中4种目标菌群无明显变化（P〉0.05）,服药后8周,粪便中大肠杆菌（4.81±0.77）lonN/g及肠球菌属（5.24±0.63）lonN/g仍无显著变化（P〉0.05）,但双歧杆菌属（8.82±0.91）lonN/g及乳酸杆菌属（6.99±0.69）lonN/g明显减少（P〈0.05）。结论长期服用质子泵抑制剂后可致肠道双歧杆菌属及乳酸杆菌属数量明显下降,使肠道生物屏障受损,增加了肠源性感染风险。