Cause Of Peptic Ulcer Disease Research Articles

Antibiotic susceptibility of Helicobacter pylori isolates in Dakar, Senegal

Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. A high frequency of H. pylori infection has been reported from resource-poor regions. H. pylori infection is curable with regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. In Africa, there are very little data concerning the susceptibility of H. pylori isolates to antibiotics. H. pylori isolates from gastric biopsies from outpatients > or = 18 years old affected by a gastro-duodenal ulcer were used in this study. Susceptibility testing was performed for amoxicillin, ciprofloxacin and metronidazole by using the Epsilometer test (E-test) method. H. pylori strains were isolated from 40 patients of whom 36 were diagnosed as having duodenal ulcer, two with gastric ulcer, and two with gastro-duodenal ulcer. Thirty-six (90%) of the isolates were resistant to metronidazole (MICs > or = 8 microg/l), whereas all isolates were susceptible to amoxicillin (MICs < or = 0.5 microg/ml) and ciprofloxacin (MICs < or = 1 microg/ml). These data suggest that metronidazole should not be used therapeutically among Senegalese patients in first-line therapy, while ciprofloxacin could be recommended in association with amoxicillin and a proton pump inhibitor in Senegal.

Peptic Ulcer Disease: Clinically Relevant Causes and Treatments

Peptic ulcer disease is a significant cause of morbidity and in certain cases mortality among affected individuals. Proper identification and treatment of peptic ulcer disease is imperative to decreasing its associated sequellae. The most common causes of peptic ulcer disease are the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and infection with Helicobacter pylori. Initial assessment of the patient with dyspepsia is paramount, as the presence of symptoms will dictate further management. With currently available treatment regimens and the ability to reduce gastrointestinal bleeding it is important for all clinicians to have knowledge of this disease, its diagnosis, and pharmacotherapy.

Helicobacter pylori eradication therapy: indications, efficacy and safety

Background: Helicobacter pylori infects up to half of the world's population. It remains the major cause of peptic ulcer disease and is recognised as a carcinogen for its role in gastric carcinogenesis. Successful eradication of the bacteria is associated with improved health outcomes including fewer dyspeptic symptoms, reduced peptic ulcer recurrence and rebleeding, reduced peptic ulcer risk with NSAIDs and as a cure for low-grade gastric MALT lymphoma. The risk of gastric cancer is reduced in those without premalignant mucosal abnormalities at the time of eradication. Objective: This review outlines the current indications and options for therapy of H. pylori with particular reference to drug-induced adverse events associated with treatment. Methods: The indications for H. pylori eradication are evidence-based and in accordance with recent consensus statements and recommendations. The eradication treatment is based on numerous clinical trials and meta-analyses. Results/conclusion: Eradication therapy, in general, is safe and well tolerated. Antibiotic therapy may be associated with significant drug adverse reactions, especially gastrointestinal symptoms.

Long-term follow-up of patients with gastric outlet obstruction related to peptic ulcer disease treated with endoscopic balloon dilatation and drug therapy

Previous studies suggest that endoscopic balloon dilatation (BD) in gastric outlet obstruction (GOO) related to peptic ulcer disease (PUD) does not achieve long-term remission and most patients require surgery. Most of these studies have not systematically attempted to alter the natural history of the underlying PUD. We reviewed our experience of management of PUD-related GOO with BD and medical treatment of PUD. The determination of the etiology of benign GOO and the assessment of long-term outcome from endoscopic BD and drug therapy. An observational study of the management of 23 consecutive patients with PUD-related GOO. A medical gastroenterology unit in the United Kingdom. Twenty-three consecutive patients with PUD-related GOO. Symptomatic and endoscopic remission of PUD and GOO. Twenty-three patients (10 men, 13 women; median age, 71 years; range, 43-94 years) presented with symptoms of GOO secondary to PUD. The initial etiologic assessment was as follows: Helicobacter pylori (12), aspirin or nonsteroidal anti-inflammatory drugs (NSAID) (3), H pylori and aspirin/NSAID (5), idiopathic (2), undetermined (1). All 17 patients who were H pylori-positive received eradication therapy. A reliable posteradication H pylori status was available in 13 and was negative in all. NSAIDs were stopped in all patients. Patients on aspirin for the prevention of atherosclerosis received concurrent antisecretory therapy (AST). In 4 patients, PUD relapsed, despite removal of initial etiology (H pylori in 3, H pylori and NSAID in 1). The PUD in these was redesignated as idiopathic, raising the number of patients with idiopathic PUD to 6. In 2 patients, remission was achieved with AST alone. Twenty-one patients underwent BD. All 23 patients remained in symptomatic remission during a median follow-up period of 43 months (range, 5-90 months). Endoscopic remission was confirmed in all but 1, who refused follow-up endoscopy. Six patients stayed in remission, without the need for maintenance AST after the underlying cause of PUD was removed. In the remaining 17 patients, maintenance AST was required for the following main reasons: idiopathic PUD (6), reflux esophagitis (6), a need for aspirin (5). Despite its small size, this study shows that treatment of PUD-related GOO by using endoscopic and medical therapy is associated with a favorable long-term outcome.

A New Helicobacter pylori Vacuolating Cytotoxin Determinant, the Intermediate Region, Is Associated With Gastric Cancer

Helicobacter pylori is the main cause of peptic ulceration and gastric adenocarcinoma. The vacuolating cytotoxin gene, vacA, is a major determinant of virulence. Two naturally polymorphic sites in vacA, the signal region and midregion, are well-characterized determinants of toxicity and markers of pathogenesis. The aim of this study was to characterize a new vacA polymorphic site, the intermediate (i) region. The vacA i-region was identified and characterized by constructing isogenic vacA exchange mutants and determining their vacuolating activity on HeLa, AGS, and RK13 cell lines. The vacA i-region types of H pylori isolates from patients undergoing routine endoscopy were determined by nucleotide sequencing and allele-specific polymerase chain reaction. Two i-region types were identified, i1 and i2, and both were common among 42 Western clinical isolates. Interestingly, only naturally occurring s1/m2 strains varied in i-type; s1/m1 and s2/m2 strains were exclusively i1 and i2, respectively. Vacuolation assays showed that i-type determined vacuolating activity among these s1/m2 strains, and exchange mutagenesis confirmed that the i-region itself was directly responsible. Using a simple i-region polymerase chain reaction-based typing system, it was shown for 73 Iranian patients that i1-type strains were strongly associated with gastric adenocarcinoma (P < 10(-3)). Finally, logistic regression analysis showed this association to be independent of, and larger than, associations of vacA s- or m-type or cag status with gastric adenocarcinoma. Together these data show that the vacA i-region is an important determinant of H pylori toxicity and the best independent marker of VacA-associated pathogenicity.

Decreasing prevalence combined with increasing eradication of Helicobacter pylori infection in the United States has not resulted in fewer hospital admissions for peptic ulcer disease‐related complications

Helicobacter pylori infection is a major cause of peptic ulcer disease, but the prevalence of this infection has been decreasing steadily. Additionally, eradication of H. pylori decreases ulcer recurrence and prevents ulcer complications such as bleeding. To examine whether the decreased prevalence of H. pylori and increased use of eradication regimens have affected the prevalence of peptic ulcer disease-related hospitalizations. We chose to study a period between 1996 and 2005. The number of gastric and duodenal ulcers as primary or secondary hospital discharge diagnoses per year for the 10-year span was collected from five large US hospitals. Collected data were analysed using Spearman correlation. No statistically significant trend was observed in the number of gastric or duodenal ulcers listed as primary or secondary discharge diagnoses at any of the five healthcare centres. Despite a decreasing prevalence of H. pylori and the increasing use of successful H. pylori eradication regimens, the prevalence of peptic ulcer disease and its complications has not changed. In the US other aetiologies, including non-steroidal anti-inflammatory drugs, may be playing a larger role than once thought.

Is perforated marginal ulcer after the surgery of gastroduodenal ulcer associated with inadequate treatment for Helicobacter pylori eradication?

A marginal ulcer developing after an initial operation for gastroduodenal ulcer is a serious threat to the patient, and a challenge to surgeons. Helicobacter pylori is the primary cause of peptic ulcer disease. However, its role in ulcer recurrence, especially of marginal ulcer (MU), after peptic ulcer surgery is unclear. This study aimed to determine any association between H. pylori infection and perforated MU by comparing the prevalence of H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) use in patients with perforated (PMU) and in those with nonperforated MU (NPMU). The study retrospectively evaluated the records of 16 patients with PMU who underwent surgical treatment and 24 patients with NPMU who underwent medical treatment in Atatürk University, School of Medicine, Department of General Surgery and Gastroenterology, between January 1995 and December 2004. The rate of H. pylori in the PMU group was significantly higher than that of the NPMU group (P < 0.01). There was a significant relationship between NSAID consumption and PMU compared with NPMU patients (P < 0.01). There was also a significant relationship between NSAID consumption and H. pylori and PMU (P < 0.01). Eradication of H. pylori after the first PMU operation especially in cases with impaired hemodynamics, severe peritoneal contamination, and/or a diameter smaller than 1 cm and avoiding the use of NSAIDs will surely reduce the risk of relapsing ulcers.

Touch cytology in diagnosing Helicobacter pylori: comparison of four staining methods

Helicobacter pylori (Hp), a major cause of peptic ulcer disease and an important risk factor for gastric malignancy, can be diagnosed by several methods. Touch cytology (TC) of the gastric mucosa has been noted to give good results and has been found to be very simple, inexpensive and rapid. However, evidence regarding the accuracy of different staining methods of TC is lacking. The present study aims at defining the diagnostic accuracy of four different staining methods of TC. Biopsy specimens were taken from the antral mucosa of one hundred consecutive patients referred for upper gastrointestinal endoscopy (UGIE) for various indications. TC slides were processed by four staining methods: Wright, Giemsa, Papanicolaou and Gram. Rapid urease test (RUT) and histological examination of specimens were also performed. The same experienced pathologist evaluated the coded samples. A patient's Hp status was established by minimum concordance of the three tests, including histology, RUT, and 'Touch mean'. The latter was defined positive when at least three of the four TC staining methods were positive. Forty-six patients (46%) were positive for Hp according to Hp status. TC stained by Wright had excellent agreement with both histology (kappa = 0.80, P < 0.001) and RUT (kappa = 0.84, P < 0.001). Regarding Hp status, histology was 100% sensitive and RUT was 100% specific. Wright-stained TC (88.89%) was significantly more specific than both Giemsa- (74.07%; P < 0.05) and Papanicolaou-stained (70.37%; P < 0.05) TC. RUT should still be acknowledged as the primary test in diagnosing Hp following UGIE. If RUT is negative and Hp detection is intended only, Wright-stained TC can safely substitute for histology. However, when assessment for severity of mucosal damage or cell atypias is meant, histology cannot be neglected.

Helicobacter pylori is invasive and it may be a facultative intracellular organism.

The pathogenicity of many bacteria colonizing the gastrointestinal tract often depends on their ability to gain access to cells that are normally non-phagocytic. Helicobacter pylori colonizes the stomach of over half the world population and is the main cause of peptic ulcer disease and gastric cancer. It is generally considered to be a non-invasive pathogen present only in the lumen of the stomach and attached to gastric epithelial cells although a number of in vivo and in vitro studies have demonstrated that H. pylori is in fact invasive. In addition, H. pylori can repopulate the extracellular environment after complete elimination of extracellular bacteria with gentamicin, suggesting it may be considered a facultative intracellular bacterium. This review examines the validity of these observations and describes the evidence suggesting that the intracellular presence of H. pylori plays a role in the induction of diseases, in immune evasion, and in life-long persistence of the bacterium in the stomach of a majority of humans.

The Prevalence of Idiopathic Peptic Ulcer and Changing Trend of Peptic Ulcer Disease and Helicobacter Pylori Infection Between 10 Years in Korea

The Prevalence of Idiopathic Peptic Ulcer and Changing Trend of Peptic Ulcer Disease and Helicobacter Pylori Infection Between 10 Years in Korea Hyun Joo Jang, Jong Pyo Kim, Cheol Hee Park, Kyung Ho Kim, Kwang Ho Baik, Il Hyun Baik, Sea Hyub Kae, Hak Yang Kim Background and Aim: Helicobacter pylori (H. pylori) infection is the main cause of peptic ulcer disease (PUD). However, H. pylori-negative and idiopathic peptic ulcer disease (IPUD) seems to be increasing in some developed countries. We studied the prevalence and clinical characteristics of idiopathic peptic ulcer disease (IPUD). We also investigated the change in the prevalence of H. pylori infection and ulcer distribution in patients with PUD during the last decade. Methods: We prospectively evaluated H. pylori infection in patients with newly diagnosed PUD by endoscopy from September 2004 to February 2005 in Hallym Medical Center. H. pylori infection was examined by rapid urease test and histology using Giemsa stain. Medical records and history taking were carefully searched for the use of NSAID or aspirin and history of previous PUD before endoscopic examination. The prevalence of H. pylori infection was compared with that of our previous results reported 10 years ago. Results: Among the 895 patients enrolled, 428 patients (47.8%) had gastric ulcer (GU), 348 (38.9%) duodenal ulcer (DU), and 119 (13.3%) both GU and DU. H. pylori infection was found in 72.0% of all patients with PUD, which consisted of 73% in GU, 68% in DU, and 79% in both GU and DU. NSAIDrelated PUD was found in 13.0% and IPUD in 22.2% of patients. Patients with IPUD showed no significant differences in clinical features compared with those with H. pylorior NSAID-related PUD. Comparing with those 10 years ago, the prevalence of H. pylori infection was not significantly changed although the proportion of DU and prevalence of H. pylori infection in DU slightly decreased. Conclusion: There was no significant change in the prevalence of H. pylori infection in PUD during the last decade. The prevalence of IPUD is not uncommon. However, the clinical features of IPUD were not significantly different with those of H. pylorior NSAIDrelated PUD. Further investigations are warranted for the clinical significance and management of IPUD.

A Humble Bacterium Sweeps This Year's Nobel Prize

Earlier this month, the Nobel Prize in Physiology or Medicine was awarded to the Australians Barry Marshall and Robin Warren for their discovery of the bacterium Helicobacter pylori and its role in peptic ulcer disease and gastric cancer. It is the first time since 1928 that the Nobel Prize has been awarded for the discovery of a bacterium, and H. pylori is the first bacterium to be associated with cancer.

Severe and Refractory Peptic Ulcer Disease: The Diagnostic Dilemma

The recognition of Helicobacter pylori infection as a cause of peptic ulcer disease, medical regimens to eradicate the organism, and the widespread use of proton pump inhibition to suppress gastric acid secretion have revolutionized the management of peptic ulcer disease. As a result, successful medical management of peptic ulcer disease has largely supplanted the need for gastric surgery by general surgeons. Surgery is reserved for complications of the disease, refractory disease, or rare causes of ulcer disease such as gastrinoma and Zollinger-Ellison syndrome. In this report, we describe a case of intractable peptic ulcer disease that progressed to gastric outlet obstruction despite maximal medical therapy. We review the diagnostic studies utilized to evaluate the potential etiologies of peptic ulcer disease and the difficulty in diagnosing gastrinoma and Zollinger-Ellison in the setting of potent medical acid suppression therapy.

Efficacy of Cranberry Juice on Helicobacter pylori Infection: a Double‐Blind, Randomized Placebo‐Controlled Trial

Helicobacter pylori infection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression of H. pylori in an endemically infected population at high risk for gastric cancer. A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 +/- 11.2 years (mean +/- SD) with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree of H. pylori infection was determined using the 13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection. A total of 189 subjects with positive 13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative 13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05). Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.

Vertical Transmission, November 2005

An ASM member wins the Nobel Prize in physiology or medicine for microbiology research done in Australia; it doesn?t come any better than that! Congratulations to Professor Barry Marshall (University of Western Australia) and his colleague Dr Robin Warren for their seminal contribution in showing that a previously unknown bacterium, Helicobacter pylori, was the major cause of peptic ulcer disease.

Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States.

Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.

The Prevalence of Peptic Ulcer not Related to Helicobacter pylori or Non‐Steroidal Anti‐Inflammatory Drug Use is Negligible in Southern Europe

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. 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. 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). 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.

Has Helicobacter pylori eradication for peptic ulcer been overrated?

Discovery of Helicobacter pylori has changed the life cycle of peptic ulcer disease (PUD). However, PUD does not completely disappear after elimination of H. pylori. Some ulcers recur even after successful eradication of H. pylori in non-users of non-steroidal anti-inflammatory drug (NSAID). In addition, the incidence of H. pylori-negative, non-NSAID PUD (idiopathic PUD) is reported to increase with time. Moreover, H. pylori-positive ulcers are not always H. pylori-induced ulcers because there are two paradoxes of the H. pylori myth: the existence of H. pylori-positive non-recurring ulcer and recurring ulcer after cure of H. pylori infection. Taken together, H. pylori is not the only cause of peptic ulcer disease. Therefore, it is still necessary to seriously consider the pathophysiology and the management of the ulcers, which may exist after elimination of H. pylori.

Lansoprazole, NSAIDs, H. pylori, and Ulcer Recurrence

Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the two most common causes of peptic-ulcer disease. Experts have debated the effect of H. pylori infection on ulcer risk in NSAID users. Investigators in Hong Kong recruited 43 patients who presented with ulcer disease …

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Comparisons were recently made between the discovery of H. pylori as a cause of peptic ulcer disease and bacterial overgrowth in IBS. This perception is based on the dramatic shift in thinking accompanying the concept that some cases of IBS may be bacterial in origin. However, the case for bacterial overgrowth in IBS may not altogether contradict the convention or negate the accumulated discoveries in IBS as a first glance may suggest. For example, it is well known that bacterial endotoxin results in rectal hyperalgesia similar to IBS (Am J Physiol 2000;279:G781–G790). The long reported psychological attributes of IBS could also have a connection to intestinal colonization because data suggest that increases in CRF, a byproduct of stress, result in a reduction of intestinal migrating motor complexes (Peptides 1986;7:73–77). A reduction in these complexes is known to result in bacterial overgrowth (J Clin Invest 1977;59:1159–1166, Ann Surg 1998;228:188–193, Dig Dis Sci 2002;47:2639–2643). Therefore, the concept of bacterial overgrowth in IBS may simply be another piece of the IBS puzzle. To address more specific concerns, there is much discussion over the efficacy of lactulose breath testing in diagnosing bacterial overgrowth. Although culture is the gold standard for most bacterial processes, given the length of the small bowel, sampling a single area is likely to underestimate the presence of bacterial overgrowth. In fact, there are tremendous limitations to small intestinal cultures, which include: (1) the lack of appropriate instruments to acquire culture specimens; (2) the low quantity of usually aspirated fluid; (3) the requirement for special techniques to preserve anaerobes; and (4) only 20% of the gut flora are even culturable (Hart AL, Stagg AJ, Graffner H, Glise H, Falk P, KammGut MA. Ecology. London: Martin Dunitz Ltd, 2002). With these limitations, indirect techniques cannot be validated against this less than perfect “gold” standard. Another concern is how bacterial overgrowth or abnormal breath testing can explain both diarrhea and constipation in IBS. Two studies now suggest an association between methane on breath test and constipation (Dig Dis Sci 2003;48:89–92, Am J Gastroenterol 2003;98:412–419). Although one possibility may be that constipation favors intestinal methanogenic proliferation, we have published data to suggest that methane gas itself may contribute. When canine small intestine is perfused with methane, a 75% reduction in transit is observed compared with transit during the perfusion with room air (Neurogastroenterol Motil 2002;4:437). Although these data are preliminary, they are very intriguing and warrant further investigation. Much of the current sentiment on this new concept in IBS has become a debate of terminology. What does an abnormal breath test mean? Is it small intestinal bacterial overgrowth? Is it colonic fermentation? More work is needed to answer these questions. However, this debate should not detract the clinical message: (1) there is a higher prevalence of abnormal breath test in IBS patients compared with controls; and (2) antibiotic treatment of IBS improves symptoms in a fashion that is highly dependent on the normalization of the lactulose breath test abnormalities (Am J Gastroenterol 2003;98:412–419).

Diagnostic methods for Helicobacter pylori detection and eradication.

Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer. The efficacy of 1 week triple therapies, which often have eradication rates of>90%, is undermined by poor patient compliance and bacterial antimicrobial resistance. The development of new anti-H. pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H. pylori. Animal models of H. pylori infection have been developed but their clinical validity has yet to be established. Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging.