Pylori-negative Ulcers Research Articles

Распределение аллелей и гаплоблочная структура полиморфизма генов матриксных металлопротеиназ у больных Н.pylori-негативной язвенной болезнью желудка и двенадцатиперстной кишки

Распределение аллелей и гаплоблочная структура полиморфизма генов матриксных металлопротеиназ у больных Н.pylori-негативной язвенной болезнью желудка и двенадцатиперстной кишки

Peptic Ulcer Disease: Maintenance treatment with H2 blockers

Peptic ulcer disease (PUD) is a prevalent disease, it affecting around 5-10% of the general population worldwide, but with notable regional and racial variations. The two most common etiological causes are the chronic infection with Helicobacter pylori (Hp) and the use of non-steroidal anti-inflammatory drugs (NSAIDs). Its diagnosis is based mainly in the endoscopy and the active search of concomitant Hp presence. The discovery of the link between H. pylori and peptic ulcer has changed dramatically its management, because it has become a curable infectious disease. The eradication therapy of is the best choice to achieve the final cure of PUD in infected patients. Several current international recommend a standard triple therapy as first-line therapy, including a proton pump inhibitor and a combination of amoxicillin and clarithromycin. This combination therapy has shown a decreased efficacy over the years. The main reason is increasing antibiotic resistance, particularly to clarithromycin and metronidazol, of certain Hp strains. Several new treatment options or modifications of already established regimens have been introduced in last years, to overcome these treatment failures. For the subgroup of patients with H. pylorinegative ulcers, avoiding NSAIDs intake also has a clear influence in evolution of the disease and in some cases drives to the complete healing of the peptic ulcer. In refractory or recurrent cases, continuous therapy with anti-secretory agents and/or the replacement of conventional NSAIDs by selective drugs for inhibition of cyclooxygenase-2 (COX-2) are useful treatment options.

Peptic Ulcer Disease

Peptic ulcer disease (PUD) is a prevalent disease, it affecting around 5-10% of the general population worldwide, but with notable regional and racial variations. The two most common etiological causes are the chronic infection with Helicobacter pylori (Hp) and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Its diagnosis is based mainly in the endoscopy and the active search of concomitant Hp presence. The discovery of the link between H. pylori and peptic ulcer has changed dramatically its management, because it has become a curable infectious disease. The Eradication therapy of Hp (+) is the best choice to achieve the final cure of PUD in infected patients. Several current international guidelines recommend a standard triple therapy as first-line therapy, including a proton pump inhibitor and a combination of amoxicillin and clarithromycin. This combination therapy has shown a decreased efficacy over the years. The main reason is increasing antibiotic resistance, particularly to clarithromycin and metronidazol, of certain Hp strains. Several new treatment options or modifications of already established regimens have been introduced few years back, to overcome these treatment failures. For the subgroup of patients with H. pylori-negative ulcers, avoiding NSAIDs intake also has a clear influence in evolution of the disease and in some cases drives to the complete healing of the peptic ulcer. In refractory or recurrent cases, continuous therapy with anti-secretory agents and/or the replacement of conventional NSAIDs by selective drugs for inhibition of cyclooxygenase-2 (COX-2) are useful treatment options.

"Gastric cytoprotection" is still relevant.

Although Andre Robert's historic article on "gastric cytoprotection" in 1979 introduced this new name and concept, gastroprotective drugs (e.g. sofalcone, sucralfate), which prevent and/or accelerate healing of gastric ulcers without inhibiting acid secretion, were known in Japan before or around that time. But since Robert's studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal research for more than 30 years. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate, despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide counteract virtually any form of gastroprotection. In Robert's terms of "prevention of chemically induced acute mucosal lesions," so far no single mechanism could explain the beneficial effects of diverse protective agents, but I argue that these two endogenous substances (i.e. PG, SH), in addition to histamine, are the main mechanistic mediators of acute gastroprotection: PG and histamine, because as mediators of acute inflammation, they increase vascular permeability (VP), and SH scavenge free radicals. This is contrary to the search for a single mechanism of action, long focused on enhanced secretion of mucus and/or bicarbonate that may contribute but cannot explain all forms of gastroprotection. Nevertheless, based on research work of the last 30 years, in part from our lab, a new mechanistic explanation of gastroprotection may be formulated: it's a complex but orderly and evolution-based physiologic response of the gastric mucosa under pathologic conditions. Namely, one of the first physiologic defense responses of any organ is inflammation that starts with rapid vascular changes (e.g. increased VP and blood flow), followed by cellular events (e.g. infiltration by acute and chronic inflammatory cells). Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. "adaptive cytoprotection"). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective, that is, a key element in the complex pathophysiologic response during acute gastroprotection. Over the years, "gastroprotection" was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence "gastric cytoprotection" research is still relevant.

Helicobacter pylori-related Peptic Ulcer Disease

Although the worldwide prevalence of Helicobacter pylori (H. pylori) infection has decreased, peptic ulcer disease (PUD) remains prevalent due to increased usage of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. In recent years, the prevalence of H. pylori infection in PUD cases and the distribution of PUD have changed in Korea. The incidence of idiopathic H. pylori-negative ulcers has increased, and research is needed to determine the cause of these idiopathic ulcers. The eradication of H. pylori infection decreases PUD recurrence, and plays a crucial role in the treatment of PUD. The H. pylori test and-treat strategy is beneficial for patients starting NSAIDs and long-term aspirin users with a history of bleeding ulcers. Although the H. pylori eradication rate is declining steadily due to antibiotic resistance, especially to clarithromycin, current guidelines still recommend standard triple therapy, including a proton pump inhibitor, amoxicillin, and clarithromycin, as a first-line therapy. Recently, various treatment regimens, including sequential or concomitant therapies, have been developed in an attempt to overcome the low eradication rate observed with standard triple therapy. The aim of this article is to review recent trends in H. pylori-related PUD, focusing on epidemiology and treatment strategies. (Korean J Med 2014;86:655-663)

More Favorable Outcomes with Peptic Ulcer Bleeding Due to Helicobacter Pylori

BackgroundAcute upper gastrointestinal bleeding is a common complication of peptic ulcer disease, often caused by Helicobacter pylori and nonsteroidal anti-inflammatory drug (NSAID) use. The purpose of this study was to determine whether the cause and biologic behavior of ulcers associated with acute upper gastrointestinal bleeding might lead to divergent patient outcomes. MethodsIn this Institutional Review Board-approved study, we compared clinical features and outcomes of patients with acute upper gastrointestinal bleeding due to ulcers categorized into 4 groups: Helicobacter pylori positive or negative combined with NSAID usage positive or negative. Likelihood chi-squared analyses were utilized for group comparisons and stepwise multiple logistic regression models were utilized to determine which factors were related to bleeding outcomes. ResultsOf 2242 patients with upper gastrointestinal bleeding, 575 (26%) had gastroduodenal ulcer disease, and of those with appropriate diagnostic testing, approximately half (228, 10% overall) had evidence of Helicobacter pylori infection and half (216, 10% overall) had no evidence of Helicobacter pylori infection. Patients without Helicobacter pylori infection had significantly more comorbid conditions than those with Helicobacter pylori and higher Charlson Index comorbidity scores (2.6 ± 2.6 [mean and SD] vs 1.9 ± 2.3, P = .003). Hospital length of stay was significantly longer for Helicobacter pylori-negative patients (mean 11.4 ± 21.7 vs 6 ± 8.5 days and median 5.5 vs 3 days, P <.001 and <.001, respectively). Rebleeding events within 30 days were more frequent in Helicobacter pylori-negative patients than Helicobacter pylori-positive patients (11% vs 5%, P = .009). Rebleeding was most frequent in patients without Helicobacter pylori and with no reported use of NSAIDS (18%, P = .01). ConclusionsHelicobacter pylori-negative ulcers were associated with poorer outcomes regardless of use of NSAIDs. Patients with ulcers negative for Helicobacter pylori and no history of NSAID use had the worst outcomes and had more severe systemic disease.

Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance

In this paper, we review the concept of quality of ulcer healing (QOUH) in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease (PUD) has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori (H. pylori), which is also the cause of ulcer recurrence. However, H. pylori-negative ulcers are present in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer recurrence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn's disease and ulcerative colitis.

Analysis of direct medical care costs of peptic ulcer disease in a Korean tertiary medical center

Objectives. There have been no reported data on the medical care cost of idiopathic peptic ulcer disease (PUD) compared with H. pylori (+) and/or NSAID (+) cases although H. pylori-negative idiopathic ulcers are increasing. The aim of this study was to investigate the direct medical care costs of PUD based on whether it was H. pylori infection/from NSAIDs or idiopathic. Material and methods. One hundred and seventy three patients with PUD comprising H. pylori and/or NSAID use-associated PUD (n = 145) and idiopathic PUD (n = 28) were prospectively enrolled in this study. The direct medical care costs were analyzed retrospectively for the patients with PUD during a one-year follow-up period. Results. The recurrence rate within one year was significantly higher in idiopathic PUD than H. pylori and/or NSAID-associated PUD (p = 0.002). Direct medical care costs of idiopathic PUD ($2483.8) were higher than in patients with H. pylori and/or NSAID-associated PUD ($1751.8) resulting from longer duration of medication and higher proportion of endoscopic hemostasis and hospitalization. Conclusions. More clinical research is needed to improve outcome and reduce recurrence rate and medical care costs of idiopathic PUD.

Helicobacter pylori–positive Versus Helicobacter pylori–negative Idiopathic Peptic Ulcers in Children With Their Long‐term Outcomes

The aim of this study is to investigate the differences in the characteristics between Helicobacter pylori-positive and H pylori-negative primary ulcers in Chinese children. We conducted a retrospective review of children with primary peptic ulcers. Demographic data, clinical presentations, endoscopic features, histological findings, H pylori prevalence, and ulcer recurrences were studied. Forty-three Chinese children with primary peptic ulcers were diagnosed over 8 years and were reviewed. There were 31 boys and 12 girls (median age 12 years, range 3-16 years). Thirty children (70%) presented with acute gastrointestinal bleeding, whereas only 19 had a history of epigastric pain. Twenty-three patients (53.5%) were H pylori positive. H pylori-positive ulcers developed in older children (median age 12 vs 10 years, P<0.05) and affected more males (91.3% vs 50%, P<0.01) than the H pylori-negative group. The annual ulcer recurrence rates were estimated to be 5.2% (95% CI 4.2-6.3) and 11.4% (95% CI 9.1-13.6) for positive and negative groups, respectively (P<0.05). Multivariate logistic regression suggested H pylori-negative status and ulcer size >1cm were indepen-dent risk factors for recurrence. Our report suggests that H pylori-negative primary ulcers exist in children with their own distinct features. In contrast to H pylori-positive ulcers, H pylori-negative ulcers develop in younger children, affect both sexes equally, and carry a higher recurrence risk.

Comparison of Clinical Characteristics and Outcomes between Geriatric and Non-geriatric Patients in Peptic Ulcer Bleeding

In geriatric patients with peptic ulcer, the use of NSAID and prevalence of chronic illness have been increased, but the Helicobacter pylori (H. pylori) infected portion decreased. The aim of this study was to evaluate the clinical characteristics and outcomes of geriatric patients (aged 65 or older) with peptic ulcer bleeding and compare with non-geriatric patients (less than 65 years old). We conducted a retrospective study of 88 patients with peptic ulcer bleeding treated with therapeutic endoscopy from January 2006 to December 2006. We compared the clinical characteristics and outcomes of geriatric patients (n=34, 38.6%) with those of non-geriatric patients (n=54, 61.4%). Hypertension (52.9% vs. 24.1%), cardiovascular disease (35.3% vs. 13.0%), and chronic obstructive pulmonary disease (20.6% vs. 3.7%) were more prevalent in the geriatric group, compared with the non-geriatric group (p<0.05). The geriatric group had taken more ulcerogenic drugs than the non-geriatric group (64.7% vs. 33.3%, p<0.05); aspirin plus clopidogrel (23.6% vs. 13.0%) and aspirin (20.6% vs. 11.0%). Sixteen (21.1%) of the 76 cases had H. pylori-negative ulcer. Between the two groups, there was no difference in the prevalence of H. pylori-negative ulcer (25.9% vs. 18.4%, p>0.05). The amount of transfusion length of ICU stay, rebleeding rate, operation rate and mortality were not different between the two groups. The length of hospital stay in the geriatric patients was significantly longer than the non-geriatric group (12.3+/-10.6 vs. 7.2+/-5.9 days, p<0.05). In multiple regression analysis, old age was a significant risk factor for longer hospital stay (p<0.05). The geriatric patients with bleeding peptic ulcer had longer hospital stay than the non-geriatric patients in our study. The important emerging etiologies such as ulcerogenic drug and associated chronic illness should be checked and treated in these patients.

Chronic Mesenteric Ischemia Presenting as Helicobacter pylori-Negative Duodenal and Gastric Ulcers. Case Report and Literature Review

Purpose: Vascular insufficiency syndromes involving arterial supply can rarely present with peptic ulceration that is unrelated to H. Pylori infection or NSAID use. Gastric ischemia is extremely rare, given the rich arterial supply to the stomach. We are reporting an 80-year-old female who presented to our hospital with approximately 10 week history of postprandial nausea, abdominal discomfort and occasional vomiting. She described the pain as dull band-like discomfort in the periumbilical region. She denied any diarrhea, constipation, melena orhematochezia. Esophagogastroduodenoscopy three weeks prior to admission revealed multiple gastric and duodenal ulcers. H. Pylori wor up was negative. Colonoscopy revealed right-sided diverticulosis. Her pain was progressively getting worse without improvement with the use of a proton-pump inhibitor. She lost 15 pounds over 3 months and had multiple visits to the emergency department. The patient had history of hypertension, hyperlipidemia and pelvic vein thrombosis. She had a history of tobacco smoking and did not consume alcohol or illicit drugs. Her medications included rabeprazole, Lipitor, Coumadin and metoprolol. She was recently taken off her Alendronate. She denied any use of corticosteroids or NSAIDs. No icterus was present. The abdomen was soft, nondistended and had normal bowel sounds. There was tenderness in the periumbilical and epigastric region to palpation without palpable masses or rebound tenderness. The patient had guaiac-negative stool. Laboratory studies revealed normal lipase, amylase and liver function tests. Gastrin concentration was 376 pg per milliliter (normal range 0–110). Abdominal CT was unremarkable. Abdominal Doppler, Abdominal MRA and later traditional angiography demonstrated occlusion of the proximal aspects of the celiac artery and superior mesenteric arteries. The patient underwent repair of her celiac and superior mesenteric axis by anterograde bypass. She tolerated the surgery well and was discharged in a stable condition. Ischemic peptic ulcer disease is seldom diagnosed. Certainly, the reconstitution of the patient's well-being after revascularization suggest that this very unusual combination was responsible for her clinical picture and the endoscopic findings. Conclusion: This case suggests that ischemia as an etiology for peptic ulcer disease should be considered in H. Pylori negative ulcers even in gastric ulcers.

Nonsteroidal Anti-inflammatory Drug Use Is a Significant Cause of Peptic Ulcer Disease in a Tertiary Hospital in Singapore: A Prospective Study

Peptic ulcers due to nonsteroidal anti-inflammatory drug (NSAID) use may have contributed to the static prevalence of ulcer disease in Asia. We aimed to determine the current etiology of peptic ulcer disease in Singapore. Consecutive patients undergoing esophagogastroduodenoscopy who had not been exposed to antibiotics, or antiulcer therapy within the past 6 months, and in whom peptic ulcers were found, were prospectively studied. Before endoscopy, patients were interviewed regarding the use of NSAID or aspirin. During endoscopy, antral biopsies were obtained for urease test and histology. Serum thromboxane B2 levels were compared with those of healthy volunteers. Peptic ulcers were detected in 600 patients during a 2-year period. The ulcers were negative for Helicobacter pylori in 212 patients (35.3%) and these H. pylori negative ulcers were related to NSAID use in 68.9% of cases. On the basis of serum thromboxane B2 levels, 30.8% of the patients with non-H. pylori non-NSAID were considered to have consumed NSAID. H. pylori negative peptic ulcer makes up a significant proportion of peptic ulcer in Singapore. Most of these ulcers were related to NSAID use. Serum thromboxane profile suggested surreptitious NSAID use in many of the non-H. pylori and apparently non-NSAID patients.

Long-term Outcome of Helicobacter pylori–Negative Idiopathic Bleeding Ulcers: A Prospective Cohort Study

Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulcers during this period were compared with that between September 1997 and August 1998. H. pylori-negative idiopathic ulcers were defined as negative tests for H. pylori, no exposure to analgesics within 4 weeks, and absence of other risk factors for ulcers. After the ulcers had healed, patients with H. pylori-negative idiopathic ulcers and patients with H. pylori ulcers who received eradication therapy were followed up for 12 months without anti-ulcer drugs. Six hundred thirty-eight patients had bleeding ulcers: 213 (33.4%) were H. pylori ulcers, and 120 (18.8%) were H. pylori-negative idiopathic ulcers (vs 480 [50.3%] H. pylori ulcers and 40 [4.2%] H. pylori-negative idiopathic ulcers in 1997-1998; P < .001). H. pylori-negative idiopathic ulcers accounted for 16.1% of patients who were admitted for bleeding and 42.4% of patients who bled while in the hospital (P < .0001); 28.3% of patients with H. pylori-negative idiopathic ulcers had histologic evidence of past H. pylori infection. The probability of recurrent ulcer complications in 12 months was 13.4% (95% CI: 7.3%-19.5%) in patients with H. pylori-negative idiopathic ulcers and 2.5% (95% CI: 0.4%-4.6%) in patients with H. pylori ulcers who received eradication therapy (P = .0002). The incidence of H. pylori-negative idiopathic bleeding ulcers is rising. These ulcers are prone to recurrent complications.

Review article: role of proton pump inhibitors in non-H. pylori-related ulcers.

The proportion of ulcers that are not associated with Helicobacter pylori infection is increasing, especially in the United States and Australia. The alarming increase in this type of ulcer warrants an analysis of the diagnostic and treatment approaches to H. pylori-negative ulcers, which was the aim of this study. The medical literature was reviewed to gather information about the prevalence, aetiology, and treatment of H. pylori-negative ulcers. The reports indicated that up to 52% of duodenal ulcers and 47% of gastric ulcers are not caused by H. pylori infection. The cause of H. pylori-negative ulceration appears to be multifactorial. Contributing factors include covert non-steroidal anti-inflammatory drug use, false-negative H. pylori tests, genetic predisposition, and in rare cases, Crohn's disease or Zollinger-Ellison syndrome. H. pylori-negative ulcers tend to be associated with hypersecretion and can have serious clinical sequelae. H. pylori-negative ulcers are often refractory to treatment, possibly because they lack the beneficial effect of H. pylori infection on antisecretory therapy. Proton pump inhibitors (PPIs) appear to effectively treat both H. pylori-positive and H. pylori-negative ulcers. We conclude that H. pylori-negative ulcers are becoming more prevalent in the United States and Australia. These ulcers may have an aggressive clinical course and can be refractory to treatment. PPI therapy is indicated for treating and preventing H. pylori-negative peptic ulcers.

Foreword

This supplement reviews state-of-the-art lectures on the latest treatment updates for Helicobacter pylori-negative ulcers and gastro-oesophageal reflux disease (GORD), and also examines challenging controversies surrounding the clinical management of dyspepsia that were addressed at the satellite symposium, ‘Acid-related Disorders in an Era of Changing H. pylori Prevalence.’ The symposium was sponsored by Takeda Chemical Industries, Ltd. and was held during the Eighth United European Gastroenterology Week in Brussels, Belgium. A faculty of seven world-recognized experts led stimulating discussions and urged the audience to participate via electronic handsets in an engaging interactive format. I presented the latest information on the alarming increase in H. pylori-negative ulcers in the United States and Australia and the best options for management of this type of ulcer. Professor Guido Tytgat, of the Uni-versity of Amsterdam, reviewed the benefits and potential risks of long-term proton pump inhibitor therapy in patients with GORD. Professor Kenneth McColl of the University of Glasgow critically examined new information concerning the management of dyspepsia patients. Professor Peter Malfertheiner, of the University of Magdeburg, moderated a stimulating interactive discussion with Professors Vincenzo Stanghellini (University of Bologna), Jean-Paul Galmiche (University Hospital CHU), and Roger Jones (Guy’s, King’s, and St. Thomas’s School of Medicine). In this innovative format, the audience was able to choose from among various options for further management of three featured cases. The panel commented on the cases and the voting results and ended each case discussion with helpful advice for the audience. Practising clinicians urgently need information and clarification in several areas regarding the role of H. pylori in acid-related disorders. It is my hope that this supplement will add to the body of knowledge in this area and aid both primary care physicians and special-ists to better manage their patients with dyspepsia.

Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers?

Recent reports in the United States have found that fewer peptic ulcers are due to Helicobacter pylori than previously believed. The aim of this study is to determine if the declining prevalence of H. pylori infection in the general population can account for the apparent increase in the frequency of non-H. pylori ulcers. A total of 396 patients with peptic ulcer or ulcer scar were enrolled in this study. The pre-1950 population consisted of 149 patients with gastric ulcers and with 44 duodenal ulcers. The post-1950 population consisted of 96 patients with gastric ulcers and 107 with duodenal ulcers. The frequency of H. pylori-negative gastric ulcers was 5.4% in patients born before 1950 and 4.2% in patients born after 1950, and the frequency of H. pylori-negative duodenal ulcers was 0% and 1.9%, respectively. There are no statistical differences between the two populations in gastric and duodenal ulcers. H. pylori seropositivity was 74.9% in asymptomatic volunteers born before 1950 and 20.7% in those born after 1950 (P < 0.01) in the general population. The attributable risk of H. pylori infection in peptic ulcer diseases was not affected by the prevalence of H. pylori infection in the general population in Japan. This suggests that the apparent increase in frequency of non-H. pylori ulcers in the United States is not simply due to the declining prevalence of infection. Other explanations for non-H. pylori ulcers should be sought.

Gastroduodenal ulcers in the Helicobacter pyloriera

The aim of the study was to evaluate the current spectrum of gastroduodenal ulcers in children referred to a regional paediatric unit in the United Kingdom. During a 5‐y period (1994–98), all children with a visibly discrete gastric and/or duodenal ulcer diagnosed at endoscopy were prospectively identified. Patients with ulcers associated with Helicobacter pylori gastritis underwent repeat endoscopy 2–3 mo after medical treatment. Thirty‐seven children, 21 boys and 16 girls of median age 11 y (range 7 mo to 16 y), had gastric and/or duodenal ulceration. Specific aetiological factors were identified in 21 of 22 with H. pylori negative ulcers, including Crohn's disease (n = 6), coeliac disease (n = 4) and treatment with ulcerogenic drugs (n = 4). Fifteen children (41%) had ulcers associated with H. pylori gastritis, including all 10 children with a chronic ulcer. Endoscopically confirmed ulcer healing was achieved in 14 of these using a 1 wk triple therapy regimen (omeprazole and a combination of two antibiotics).In conclusion, the recognized spectrum and the management of gastroduodenal ulceration have changed during the last decade. Although H. pylori gastritis is an important aetiological factor, a wide range of other conditions needs to be considered. Surgical intervention is only rarely necessary.

Helicobacter pylori: Past, present and future

Much has been achieved in Helicobacter pylori research, to the point that the growth of new knowledge is bound to slow down. However, expectations for further developments remain high. Knowledge about the characteristic organism and behaviour is already extensive. Particularly intriguing are the differences in genetic make-up in the various geographical regions. Sadly, detailed knowledge on how the organism spreads is still lacking. The spectrum of clinical presentation in humans is largely known. Helicobacter pylori is disappearing worldwide, allowing the relative frequency of H. pylori-negative ulcer disease to increase. The extent to which H. pylori disappearance and eradication is responsible for decreasing prevalence of gastric cancer remains speculative. Antimicrobial therapy is dominated by proton pump inhibitor triple therapy as first line therapy, with quadruple therapy as second rescue line therapy. The long-term consequences of the rising resistance to the 'key' antimicrobials are so far unknown, because few data are available on therapeutic outcomes in routine practice outside pharmaceutical trials.

Review article: Helicobacter pylori: where are we and where are we going?

This paper contains a personal view on what has been achieved in Helicobacter pylori research and what the expectations might be for further developments. Knowledge about the organism is already extensive. Particularly intriguing are the differences in genetic make-up in the various geographical regions. Sadly, detailed knowledge on how the organism spreads is still lacking. The clinical spectrum of the disease in man is largely known, but as H. pylori is disappearing worldwide, the relative frequency of H. pylori-negative ulcer disease is increasing. To what extent H. pylori disappearance and eradication is responsible for the decreasing incidence of gastric cancer remains uncertain. Antimicrobial therapy is dominated by proton pump inhibitor triple therapy as first line with quadruple therapy as second-line therapy. The long-term consequences of the rising resistance to the 'key' antimicrobials are so far unknown and speculative.

Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population

Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status of H. pylori infection in the background population may influence the incidence of H. pylori-negative peptic ulcer disease. To examine the incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs in Japan. A total of 398 patients who had no eradication therapy for H. pylori prior to this study, including 246 patients with gastric ulcer (GU) and 152 patients with duodenal ulcer (DU), were enrolled. H. pylori status was assessed by rapid urease tests, histological examinations (haematoxylin & eosin stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy specimens were taken from the antrum within 3 cm of the pyloric and two from the middle corpus of the stomach, along the greater curvature. Patients were asked a series of questions regarding risk factors, including the use of NSAIDs. The presence of gastritis, gastric atrophy and intestinal metaplasia was examined according to the updated Sydney system. Of the 246 patients with GU, 12 patients (4.9%) were considered to be H. pylori-negative. Of the 152 patients with DU, two patients (1.3%) were considered to be H. pylori-negative. Hence, a total of 14 patients were found to be H. pylori-negative. Nine of them were taking NSAIDs. Consequently, the frequency of H. pylori-negative ulcer without intake of NSAIDs was 1.3%. There was no significant difference in the frequencies of H. pylori-negative patients between the GU and DU groups. The incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs was very low in the Japanese population.