Interaction of Helicobacter pylori Infection and Nonsteroidal Anti‐Inflammatory Drugs in Gastric and Duodenal Ulcers

Background: Gastric (GU) and duodenal ulcers (DU) are in most instances either induced by Helicobacter pylori infection or by nonsteroidal anti‐inflammatory drugs (NSAIDs). Whether eradication of H. pylori is beneficial in NSAID users for preventing NSAID induced GU and DU has been the focus of different studies. Materials and Methods: Mechanisms shared by both H. pylori and NSAIDs for the induction of GU and DU were reviewed and randomized controlled trials on H. pylori eradication for prevention and healing of GU and DU in patients requiring NSAID therapy were identified by a PubMed search. Results: Key factors in the induction of GU and DU for both H. pylori and NSAIDs are a decrease in pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonucleates in distinct compartments. For primary ulcer prevention, H. pylori eradication before starting an NSAID therapy reduces the risk of NSAID induced GU and virtually abolishes the risk of DU. H. pylori eradication alone is not sufficient for secondary prevention of NSAID induced GU and DU. H. pylori infection appears to further increase the protective effects of proton‐pump inhibitors (PPI) to reduce the risk of ulcer relapse. H. pylori eradication does not influence the healing of both GU and DU if NSAID intake is discontinued. Conclusions: Duodenal ulcer is more closely related to H. pylori infection than GU in NSAID users. H. pylori eradication is recommended for primary prevention of GU and DU in patients requiring NSAID therapy. PPI therapy is mandatory for secondary prevention of gastroduodenal ulcers, and appears to further reduce the risk of ulcer relapse in the presence of H. pylori.     

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients

Objective. Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. Methods. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori‐cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Results. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Conclusions. Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.     

Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis

Aim: To investigate the association between use of nonsteroidal anti‐inflammatory drugs (NSAID) and Helicobacter pylori infection, interactive effect of H. pylori infection and NSAID use on the development of peptic ulcer disease (PUD), and the effect of H. pylori eradication therapy on PUD development. Material and Methods: We performed a systematic literature search in EMBASE and PubMed for relevant articles published in English between January 1989 and August 2010, with the following MeSH and/or key words: non‐steroidal anti‐inflammatory drugs, or NSAIDs, Helicobacter pylori, or H. pylori, peptic ulcer disease or PUD, and randomized‐control study or clinical trial. The meta‐analysis was conducted using the Review Manager 4.2.2. Results: In the analysis of five studies, the pooled prevalence of H. pylori infection was 74.5% and 71.1% in NSAID users and non‐NSAID users, respectively, (OR = 0.65; 95% CI: 0.35–1.20, p = .170). In the analysis of nine studies, the pooled prevalence of PUD in NSAID users was 31.2% and 17.9% in the presence and absence of H. pylori infection, respectively, (OR = 3.08; 95% CI: 1.26–7.55, p = .010). Moreover, in the analysis of seven studies, PUD developed in 6.4% and 11.8% of NSAID users with and without eradication therapy, respectively (OR = 0.50; 95% CI: 0.36–0.74, p < .001). The preventive effect of the eradication therapy was further revealed in NSAID‐naive users (OR = 0.26; 95% CI: 0.14–0.49, p < .0001) and in the Asian population (OR = 0.30; 95% CI: 0.16–0.56, p < .001). Conclusion: NSAID use is not associated with H. pylori infection in patients with PUD. PUD is more common in H. pylori positive than in negative NSAID users. Moreover, H. pylori eradication therapy reduces PUD incidence in NSAID users, especially in naive users and in the Asian population.     

Systematic review and meta-analysis: Helicobacter pylori eradication therapy after simple closure of perforated duodenal ulcer

Background: The most common complications of peptic ulcer are bleeding and perforation. In many regions, definitive acid reduction surgery has given way to simple closure and Helicobacter pylori eradication. Aim: To perform a systematic review and meta‐analysis to ask whether this change in practice is in fact justified. Materials and Methods: A search on the Cochrane Controlled Trials Register, Medline, and Embase was made for controlled trials of duodenal ulcer perforation patients using simple closure method plus postoperative H. pylori eradication therapy versus simple closure plus antisecretory non‐eradication therapy. The long‐term results for prevention of ulcer recurrence were compared. Results: The pooled incidence of 1‐year ulcer recurrence in H. pylori eradication group was 5.2% [95% confidence interval (CI) of 0.7 and 9.7], which is significantly lower than that of the control group (35.2%) with 95% CI of 0.25 and 0.45. The pooled relative risk was 0.15 with 95% CI of 0.06 and 0.37. Conclusions: Helicobacter pylori eradication after simple closure of duodenal ulcer perforation gives better result than the operation plus antisecretory non‐eradication therapy for prevention of ulcer recurrence. All duodenal ulcer perforation patients should be tested for H. pylori infection, and eradication therapy is required in all infected patients.     

Peptic ulcers and erosions are common in Israeli children undergoing upper endoscopy

Background: Peptic ulcers and erosions (PU&E) are thought to be uncommon in children. Patients with early exposure to Helicobacter pylori may be at a higher risk for early onset PU&E. Children in Israel have a high prevalence and early acquisition of Helicobacter pylori (H. pylori) and have easy access to pediatric gastroenterologists and endoscopy. Our aim was to describe the prevalence and characteristics of PU&E in this population referred by Pediatric Gastroenterologists for an upper endoscopy. Methods: We conducted a retrospective study over the years January 2003–May 2006. Over these years we had information on 751 diagnostic upper endoscopies. PU&E was regarded as erosive gastritis/duodenitis or ulcer in either the stomach or duodenum. H. pylori status was assessed using rapid urease test and gastric biopsies. Results: PU&E was detected in 169 (22.5%) patients (ulcers 51 (6.8%), erosions 118 (15.7%)). One hundred twenty‐four had gastric PU&E and 58 had duodenal PU&E. H. pylori was positive in 112 (66.3%). H. pylori‐associated PU&E becomes common after age 10 years, with gastric PU&E presenting much earlier than duodenal disease. Most of the H. pylori‐negative PU&E were idiopathic and improved symptomatically on PPI treatment. Interestingly, 43% of patients with PU&E in our cohort were either immigrants from the former Soviet Union or of Israeli Arab origin. Conclusions: PU&E appears to be common in this selected population with a relatively high incidence of gastric PU&E. H. pylori associated PU&E becomes common after age 10 years with gastric PU&E presenting much earlier than duodenal disease. Non H. pylori PU&E in children comprises approximately a third of all PU&E, are mostly idiopathic and appear earlier than H. pylori associated PU&E.     

Double-blind, Multicenter, Placebo-Controlled Evaluation Of Clarithromycin And Omeprazole For Helicobacter Pylori-Associated Duodenal Ulcer

Background. Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. Materials and Methods. The aim of this double-blind, randomized, multicenter (n=30), multinational (n=10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. Results. Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n=102) or omeprazole and placebo (n=106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%–82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%–6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%–19%) of dual therapy recipients, compared with 50% (39%–61%) of those who took omeprazole alone (p <.001). Conclusion. Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.     

Normalization of phospholipids concentration of the gastric mucosa was observed in patients with peptic ulcer after eradication of Helicobacter pylori

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer. Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin. Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication. Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.     

Helicobacter pylori infection,mucosal atrophy and intestinal metaplasia in Asian populations: a comparative study in age-, gender- and endoscopic diagnosis-matched subjects

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races. Materials and Methods. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori‐related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori‐positive cases (n = 120, 109, 145, 80, respectively) and H. pylori‐negative cases (n = 55, 66, 30, 95, respectively). Results. Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori‐positive Japanese subjects than in H. pylori‐positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori‐negative subjects belonging to the different Asian populations examined. Conclusions. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.     

Gastric mucosal blood flow changes in Helicobacter pylori infection and NSAID-induced gastric injury

Background. The impact of H. pylori infection on gastric mucosal blood flow and NSAID‐induced gastric damage is unclear. Aim. To study the effects of H. pylori infection on gastric mucosal blood flow, both at basal conditions and after NSAID exposure, and its relation with mucosal damage and nitric oxide production. Methods. Gastric mucosal blood flow, nitric oxide production and gastric damage were assessed in time after H. pylori SS1 or E. coli inoculation in mice. Experiments were conducted in basal conditions or after oral exposure to indomethacin (20 mg/kg). Results. H. pylori infected mice exhibited a significant increase in gastric blood flow and gastric nitric oxide production 1 week after infection, but those parameters returned to basal levels by 4 weeks. NSAID challenge elicited a similar reduction in gastric blood flow [25–35%] in H. pylori‐infected and control animals. However, only 1 week H. pylori‐infected mice, which exhibited a significant baseline hyperemia, were able to maintain gastric blood flow values within the normal range after NSAID exposure. NSAID‐induced gastric damage was increased in H. pylori‐infected mice by 4 weeks, but not 1 week after infection. Conclusions. Underlying H. pylori infection aggravates acute NSAID‐induced gastric damage. However, at early phases, gastric hyperemia associated with increased nitric oxide production may exert some protective role.     

Interactions Among Gastric Somatostatin, Interleukin-8 and Mucosal Inflammation in Helicobacter pylori-Positive Peptic Ulcer Patients

Background. To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin‐8 (IL‐8), histological inflammation through eradication therapy, and interactions among these parameters. Methods. Twenty‐eight H. pylori‐positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and ¹³C‐urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL‐8 were measured by radioimmunoassay and enzyme‐linked immunosorbent assay, respectively. Histology was assessed by the Sydney system. Results. H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients’ backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL‐8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL‐8. Conclusions. These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide‐immune interactions in the gastric mucosa exist in H. pylori infection.     

Eradication of Helicobacter pylori does not reduce the incidence of gastroduodenal ulcers in patients on long-term NSAID treatment: double-blind, randomized, placebo-controlled trial

BACKGROUND: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. OBJECTIVE: To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. METHODS: Patients on long-term NSAID treatment and who are H. pylori positive on serologic testing, were randomly assigned to either H. pylori eradication (omeprazole, amoxicillin, and clarithromycin) or placebo. Primary endpoint was the presence of endoscopic gastric or duodenal ulcers 3 months after randomization. RESULTS: One hundred sixty-five (48%) of a total of 347 patients were on gastroprotective medication. At endoscopy, gastroduodenal ulcers were diagnosed in 6 (4%) and 8 (5%) patients in the eradication and placebo group, respectively (p = .65). During follow-up of 12 months, no symptomatic ulcers or ulcer complications developed. No significant differences were found in the development of gastroduodenal erosions, dyspepsia, or in quality of life. CONCLUSION: H. pylori eradication therapy in patients on long-term NSAID treatment had no beneficial effect on the occurrence of ulcers, erosions, or dyspepsia. Ulcer rates in both study arms are remarkably low, in both patients with and without gastroprotective therapy.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Acid inhibitory potency of twice a day omeprazole is not affected by eradication of Helicobacter pylori in healthy volunteers

Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. Materials and Methods. We undertook 24‐hour pH‐metry in 12 H. pylori‐positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H⁺ concentration‐time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL‐1α, IL‐8, IL‐13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H⁺ concentration‐time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori. Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.     

The functional status of the Helicobacter pylori sabB adhesin gene as a putative marker for disease outcome

Background. Helicobacter pylori factors that contribute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. Expression of the outer membrane proteins OipA, HopZ, SabA, and SabB is regulated by phase‐variable dinucleotide repeats in the coding regions of the respective genes. We have evaluated the correlation between the expression status of these four genes and disease outcome of H. pylori infection in a Dutch patient population. Materials and Methods. H. pylori strains, isolated from 96 Dutch patients with gastritis (n = 29), duodenal ulcer (n = 28), gastric ulcer (n = 21), gastric carcinoma (n = 9), and lymphoma (n = 9), were analyzed for the ‘on/off’ expression status of the H. pylori genes oipA, hopZ, sabA, and sabB by direct DNA sequence analysis of amplified fragments. Results. The off‐status of sabB was significantly associated with duodenal ulcer (p = .036), but not with gastric ulcer. In contrast, the expression status of oipA, hopZ, and sabA did not correlate with disease outcome. Furthermore, lymphoma strains appeared to express a significantly smaller amount of putative adhesins when compared to gastritis, gastric ulcer, duodenal ulcer and gastric carcinoma strains (p < .02 for all groups tested). Conclusion. The off‐status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assuming that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system.     

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children

Background. Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal‐stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods. Thirty‐six children aged 10–17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2–3 months after H. pylori eradication. Meal‐stimulated serum gastrin response was assessed before and 12 months after eradication. Results. H. pylori gastritis was typically antrum‐predominant. Acid secretion was greater in H. pylori‐positive patients with duodenal ulcer than in gastritis‐only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori‐positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre‐ and post‐H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal‐stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions. H. pylori infection in children is associated with a marked but reversible increase in meal‐stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.     

The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage

NSAIDs are prescribed widely but have rare serious gastrointestinal side effects. More recently, adverse cardiovascular effects of these drugs have also been recognized, leading to the withdrawal of some agents and continuing uncertainty about the best approach for patients requiring NSAID therapy. Proton pump inhibitors (PPIs) provide potent and long-lasting inhibition of gastric acid secretion and have proven efficacy in healing NSAID-associated ulcers, including those with continued exposure to NSAIDs. PPIs have also shown efficacy in reducing the risk of ulcerations due to NSAID use compared with NSAIDs alone in randomized controlled trials (RCTs) where endoscopic ulcers are used as the primary endpoint, albeit a surrogate marker for clinical ulcers and complications. Large RCT outcome trials comparing patients exposed to NSAIDs with and without PPI co-therapy have not been performed, but adequately powered RCTs in high-risk patients demonstrate that PPI + nonselective NSAID provides similar rates of symptomatic ulcer recurrence rates as the use of a cyclooxygenase (COX)-2 selective inhibitor. A RCT in high-risk patients with previous ulcer complications supports the additive bene3 t of two risk-reducing strategies, as ulcer complication recurrence was eliminated in high-risk patients who were given a COX-2 selective agent with a PPI. Helicobacter pylori, an independent risk factor for ulcers, should be sought out and eradicated in patients at increased gastrointestinal risk, typically those with an ulcer history. Following H. pylori eradication, however, patients remain at risk and co-therapy with a PPI is recommended. NSAID medication selection should consider both the individual patients' gastrointestinal and cardiovascular risks.     

Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis

Background. Cyclooxygenase (COX)‐2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis. Materials and Methods. Gastric biopsies from 160 subjects, 97 with nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with gastric cancer were examined immunohistochemically for COX‐2 expression, cell proliferation and apoptotic indices. Results. COX‐2 expression in corpus was significantly higher in H. pylori positive than in negative non‐ulcer dyspepsia (NUD) (p < .05). Regardless of site, gastric cancer subjects had higher COX‐2 expression in both antrum and corpus compared with H. pylori negative and positive NUD (p < .005). Proliferation was higher in cancer and H. pylori positive than in negative NUD (p < .0001). Moreover, cancer had enhanced proliferation than H. pylori positive NUD in corpus greater (p = .0454) and antrum lesser (p = .0215) curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p < .05). However, both had a higher index than the cancer subjects (p < .0001). Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than in positive NUD in greater (p = .0122) and lesser (p = .0009) curvatures. However, both had a higher A:P ratio than cancer cases (p = .0001). A negative correlation between COX‐2 expression and A:P ratio was found in corpus greater (r = –.176, p= .0437) and lesser (r = –.188, p= .0312) curvatures. Conclusion. The expression of COX‐2 is associated with disruption in gastric epithelial kinetics and hence may play a role in gastric carcinogenesis.     

What To Do About Helicobacter pylori? A Decision Analysis of its Implication on Public Health

Objectives. Public health measures to eradicate Helicobacter pylori in the general population may prevent the occurrence of nonulcer dyspepsia (NUD), peptic ulcer (PUD) and gastric cancer, but may at the same time increase the prevalence of gastroesophageal reflux disease (GERD). A decision analysis is carried out to quantify the counteracting influences of H. pylori and resolve the controversy about a public policy to eliminate H. pylori from the general population. Methods. A compartment model is structured to analyze the jointly beneficial and adverse effects of H. pylori. Gastric acid, H. pylori infection, and other pathophysiological mechanisms influence the occurrence of reflux disease, peptic ulcer and dyspepsia, which all contribute to the occurrence of upper abdominal symptoms. Each influence is modeled as a separate compartment with various connections to other compartments. The simulation is carried out on an electronic spreadsheet. Results. A decision in favor or against eradication of all H. pylori depends primarily on the relative contribution of reflux disease vs. peptic ulcer and dyspepsia to upper abdominal symptoms in the general population. If reflux‐related symptoms contribute twice more than peptic ulcer plus dyspepsia to the overall occurrence of abdominal symptoms, a strategy to eradicate H. pylori would actually lower rather than raise public health. Below this threshold such strategy may improve general well‐being. In the individual patient infected with H. pylori, it remains beneficial to eradicate H. pylori, irrespective of the symptoms’ nature. Conclusions. Although it is advisable to treat H. pylori infection in the individual patient who comes to medical attention, a general policy directed towards complete elimination of H. pylori from the population would not be beneficial. A compartment model provides a simple yet powerful method to assess complex disease behavior.     

The effects of nocturnal acid breakthrough on Helicobacter pylori eradication

Background. The effects of nocturnal gastric acid breakthrough (NAB) on Helicobacter pylori eradication are still unknown in peptic ulcer patients. The purposes of this study were to compare the effect of lansoprazole 30 mg twice a day (bid) to lansoprazole 60 mg once a day (qd) on the prevalence of NAB, and to determine whether NAB affects the eradication of H. pylori in peptic ulcer patients. Methods. Experiments were carried out in 67 patients with H. pylori‐positive peptic ulcers. They were randomized into two groups, one treated with a combination of lansoprazole 60 mg, clarithromycin 1.0 g, and amoxycillin 2.0 g once a day before breakfast (qd group), and the other, divided doses of the drugs were given before breakfast and dinner (bid group) for 2 weeks. Results. NAB occurred in 31 patients, 55.2% in qd group, and 39.5% in bid group (p = .226). H. pylori eradication was achieved in 61.3% in NAB positive group and 83.3% in NAB negative group (p = .055). The mean duration of NAB for H. pylori eradication group was 99.3 ± 22.7 min, and 293.2 ± 49.8 min for H. pylori persistence group (p < .05). The median intragastric pH of the H. pylori eradication and persistence group was 5.7 ± 0.2 and 4.2 ± 0.4, respectively (p < .05). Conclusions. Neither the morning dose and the divided dose regimen of lansoprazole affected the intragastric acidity and occurrence of the NAB. NAB did not influence H. pylori eradication in peptic ulcer patients, but the duration of NAB and total intragastric median pH were found to influence the H. pylori eradication.     

Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic ulcer bleeding

Background and Aims: To assess the validity of biopsy‐based tests (histology, culture, and urease test) and serology in detecting current H. pylori infection for the peptic ulcer patients who had gastric bleeding. Methods: A total of 398 peptic ulcer patients were enrolled and divided into two groups, according to the presence or absence of bleeding. The diagnosis for current H. pylori infection was verified using the gold standard combining individual H. pylori tests. Sensitivity, specificity, and positive and negative predictive values of the culture, Campylobacter‐like organism (CLO) test (urease test), histology, and serology were compared. Results: Of the total study population (N = 398), 157 (39.4%) patients were categorized into the bleeding group. The sensitivities of the culture (40.0%) and CLO (85.0%) in the bleeding group were significantly lower than culture (58.1%) and CLO (96.4%) in the nonbleeding group (p = .012 and p < .001, respectively). In the bleeding group, the sensitivity of CLO (85.0%) was significantly lower than histology (92.5%) and serology (97.4%) (p = .013 and p = .002, respectively), which was not found in the nonbleeding group. The specificity of serology in the bleeding group (56.3%) was significantly lower than that of nonbleeding group (74.2%) (p = .038). Similarly, the specificity of serology was significantly lower than the other H. pylori tests in the bleeders. Conclusions: Bleeding decreased the sensitivity of H. pylori tests in patients with peptic ulcer, especially in urease test or culture. In contrast, histology was found to be a quite reliable test, regardless of the presence of bleeding.