Upper Gastrointestinal Diseases Research Articles

Prevalence of Helicobacter pylori vacA, cagA and iceA genotypes in South African patients with upper gastrointestinal diseases

Clinical response to Helicobacter pylori infection may be determined by specific virulence-associated genotypes which varies geographically. The aim of this study was to investigate the diversity of putative virulence markers of H. pylori; cagA, vacA and iceA in the Eastern Cape Province of South Africa. One hundred H. pylori strains obtained from dyspeptic patients were used. Gastric biopsies were obtained from 254 dyspeptic patients. H. pylori was cultured and strains were studied. Bacterial genotypes cagA, vacA (s and m subtypes) and iceA were analysed by PCR using specific primers. CagA was identified in 90% of the strains investigated. Fifty-eight of the 100 strains had the vacA signal sequence genotype s1 and 26 had subtype s2. Combined vacA s1/s2 was detected in 16 of the strains. VacA middle region analysis showed that 8 (8%) strains were m1 while 50 were m2. Combined vacA m1/m2 was detected in 36 of the strains. s1m2 (20%) and s2m2 (20%) genotypes were the most common allelic combinations of the vacA gene among the strains. Multiple vacA genotypes were detected in this study. Twenty-six percent of the strains identified had both iceA1 and iceA2. All our strains tested positive for the ureC (glmM) gene. This study reveals a high prevalence of vacA, cagA and iceA2.

Oesophageal and gastric cancer awareness

National oesophago-gastric cancer awareness week has recently been held to highlight the importance of early detection of upper gastrointestinal disease. Dawn Elliot outlines the aims of the campaign.

W1019 Changes in Prevalence of Upper Gastrointestinal Disease Detected at Endoscopy – From the Age of Peptic Ulcers and Gastric Cancer to the Age of Reflux Esophagitis

W1019 Changes in Prevalence of Upper Gastrointestinal Disease Detected at Endoscopy – From the Age of Peptic Ulcers and Gastric Cancer to the Age of Reflux Esophagitis

Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort

The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.

Gastric juice acidity in upper gastrointestinal diseases

To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases. Fasting gastric juice acidity of 165 healthy subjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination. Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively. Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice.

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort

Objective To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates.Design Nested case-control analysis within a primary care...

Correlates shift work with increased risk of gastrointestinal complaints or frequency of gastritis or peptic ulcer in H. pylori-infected shift workers?

There is an ongoing discussion whether work under shift work conditions enhances the ulcerogenic potential of Helicobacter pylori infections. This may be induced by a disruption of the circadian rhythm. The present study assessed whether there is an association between H. pylori infection and an increased risk of gastrointestinal complaints or frequency of gastritis or peptic ulcer in H. pylori-infected shift workers. We analyzed 615 workers divided in shift and daytime. Upper gastrointestinal diseases, medication or operation, unspecific gastrointestinal complaints, smoking habits, subjective job strain and private stress factors were monitored. The H. pylori status was analyzed using IgA and IgG antibody concentration in blood and qualitative ELISA for feces. It was observed that 27.6% of all workers, 34.6% of the shift workers and 16% of daytime workers were Hp positive (P = 0.004). Shift workers reported reflux or pyrosis less frequently than daytime workers. No increased lifetime prevalence for gastritis, ulcus or eradication therapy was found for shift workers. Analysis revealed a weak regression between age and Hp-positive gastritis or upper gastrointestinal complaints, smoking habits were a major confounding factor for ulcus disease. Clinical manifestation of gastritis or ulcus disease did not correlate with shift work or especially shift work including night work. As a result of the present study, it cannot be confirmed that there is a causal connection between shift work and upper or unspecific gastrointestinal complaints or gastritis or peptic ulcer in dependency of a H. pylori colonization.

Burden of Digestive Diseases in the United States Part I: Overall and Upper Gastrointestinal Diseases

Introduction to Series Digestive, liver, and pancreatic diseases have a far-reaching medical, economic, social, and political impact on society in the United States and worldwide. We believe it is important to highlight salient features as well as key tables/figures from the Burden of Digestive Diseases in the United States report developed as part of the National Commission on Digestive Diseases of the National Institutes of Health. The commission was created, in part, due to the advocacy efforts of the AGA. Divided into three segments, this series, spanning consecutive issues in Gastroenterology, will be informative and illuminating. The series will provide investigators, clinicians, and other readers with the necessary tools to generate new hypotheses, craft new directions of broad-based and integrated research, and make informed clinical conclusions. Hashem B. El-Serag, Associate Editor Anil K. Rustgi, Editor

Helicobacter pylori Antigenemia in an Asymptomatic Population of Eastern Cape Province, South Africa: Public Health Implications

Helicobacter pylori is a major cause of such upper gastrointestinal diseases as gastritis, peptic ulcer, and gastric cancer. The risk of infection is increased in those living in the developing world, which has been ascribed to precarious hygiene standards, crowded households, and deficient sanitation common in this part of the world. Fecal samples were collected from 356 apparently healthy subjects, consisting of 168 males and 188 females aged from 3 months to > or = 60 years (Mean = 31 years). A standardized questionnaire describing demographic characteristic including age, sex, household hygiene, socioeconomic status, and so on was applied. A sandwich-type enzyme immunoassay amplification technology (Amplified IDEIA Hp StAR, Oxoid, UK) was used to analyze the fecal samples for the detection of H. pylori antigens using monoclonal antibodies specific for H. pylori antigens. Fisher's exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. Odds ratio (OR) and the corresponding 95% confidence interval (CI) were calculated to measure the strength of association using EPI INFO 3.41 package. P values of < .05 were required for significance. H. pylori antigen was detected in 309 of the 356 subjects giving an overall prevalence of 86.8%. Prevalence increased with age from 75.9% in children < 12 years age to 100% in young adults aged 25-47 years and subjects aged > or = 60 years (P < .05). H. pylori prevalence was higher in females than in males. Of 188 females who participated in the study, H. pylori antigen was detected in 172 (91.5%) versus 144 (85.7%) 168 males (P > .05). Interestingly, H. pylori antigen was detected more often (100%) in the high socioeconomic group than in those of low socioeconomic group (85.9%) (P > .05). The results of this study have revealed a high prevalence of H. pylori antigens in fecal samples of asymptomatic individuals in the Nkonkobe municipality, an indication of active infection. Socioeconomic status, contaminated water, and poor sanitation may play a role in H. pylori transmission in this population. This finding is of public health and epidemiologic significance.

Evidence of an inverse relationship between cytotoxin-associated gene A-positive Helicobacter pylori infection and oesophageal adenocarcinoma and possible geographical implications

Over the past 50 years there have been marked changes in the prevalence of upper gastrointestinal diseases in the Western world. Oesophageal adenocarcinoma (OAC) is the most rapidly increasing cancer in the United States today and is increasing at the rate of ~10% each year in the developed world. It is predicted that if this trend goes unchecked OAC will become the predominant cancer of this century. This type of cancer is usually preceded by gastro-oesophageal reflux disease (GORD) and a pre-cancerous condition known as Barrett’s metaplasia in which columnar epithelial cells of the lower oesophagus grow abnormally and show metaplastic changes.1

Thyroid cancer in a pediatric patient affected by ulcerative colitis

iopsy for a suspicious upper gastrointestinal disease. In all f them serum sample were assayed for IgG antibodies to agA and ABO blood groups were determined by standard echniques. Results. 19 children (76%) were Hp positive by istopathology and urease rapid test. 15 of these 19 (79%) p positive patients were positive for CagA serology, too. At ndoscopic examination of the 19 infected children, hypermia and friability of the gastric antrum was observed in (37%) patients and antral nodularity appearance in 12 63%) children. The histologic examination of all infected atients showed an active microerosive gastritis and chronic astritis. The children CagA positive presented more intense yperemia of gastric antrum, associated to an important lymhoplasmacellular infiltrate and a degenerative and vacuolar esions. The 6 (24%) non-infected patients, also negative for agA serology, had a normal gastric finding but they preented cardial hyperemia and distal oesophageal erosions. We ound that seropositivity for Hp increased with age and the ate of Hp infection was not significantly different in boys and irls. Similarly, Hp serological status was not significantly ifferent between subjects of different ABO blood groups. Conclusion. Endoscopic finding of antral nodularity and ositive CagA serology suggest the presence of Hp infecion and are important markers of severe gastritis. Despite pidemiological evidence of increased peptic ulcer disease n ABO blood group O subjects, we found no association etween Hp infection and ABO blood groups.

Identification of the repeated number of C and D regions of tyrosine phosphorylation motifs in Helicobacter pylori cagA using multiplex PCR

Various tyrosine phosphorylation motif regions of H. pylori cagA exist. The number of these regions was found to have some influence on cell signaling, which was found to be more pronounced when in D (ESS) region than in C (WSS) region. A molecular biological method with multiplex PCR was developed to distinguish C and D regions, and to identify the repetition number of tyrosine phosphorylation of the cagA gene. Multiplex PCR using novel primer sets was performed on 73 strains of H. pylori isolated from Korean patients with upper gastrointestinal diseases. The Western cagA was identified in only 3 strains (4.1%) whereas East Asia cagA was identified in 69 strains (94.5%). These results were reconfirmed through a sequencing analysis. The method developed in this study would be useful for monitoring the repeated number of C and D regions of tyrosine phosphorylation motifs in H. pylori cagA.

Hepatopancreaticobiliary (HPB) Surgery: What Is the Right Fellowship for the Right Training?

Reduced resident work hours over the last several years have led to inadequate exposure to hepatopancreaticobiliary (HPB) and complex upper gastrointestinal (UGI) surgical procedures. Therefore, residents are seeking additional training in this field. The purpose of this study is to determine the role of a new fellowship model in the training of general surgery residents in complex HPB/UGI diseases. We propose a surgical training model in benign as well as malignant diseases of the UGI tract. The proposed model would focus on an integrated approach that involves allied specialties such as gastroenterology (GI) and radiology. The fellowship was set as 1-year duration with 1-month rotations on interventional GI and transplantation. The fellow spent the remaining 10 months on a UGI laparoscopic and open surgery service caring for complex benign and malignant disease of the esophagus, stomach, bile duct, pancreas, and liver. Didactic conferences were focused specifically at an organ-based approach to diseases of these organs. During a 12-month fellowship, exposure to complex diseases of the UGI tract was accomplished without negatively impacting the general surgery residency program. This new mode of advanced training provides a bridge between surgical oncology and transplantation, and it is an excellent model for postgraduate surgical training in UGI diseases.

OXYSTEROLS INFLUENCE HEPATIC CELLS HOMEOSTASIS

gastric mucosa due to H. pylori infection may result in decreased numbers of ghrelin producing cells and lower plasma ghrelin levels [7,9]. In contrast, there was not significant difference in plasma ghrelin levels between H. pylori infected patients and H. Pylori uninfected patients in our study; 32,56±21,97 and 34,04±20,59 respectively (p:0,75), similar with another Turkish study [8]. In conclusion, according to our results, there is not a relation between plasma ghrelin levels and H. pylori infection. These conflicting results may be related to different H. pylori strains, as in Turkey the prevalence of the strains, such as CagA, that cause atrophic gastritis is lower [11]. Moreover; differences in studied populations in terms of race, sample size, nutritional status and habits can also affect results. Decreasing plasma ghrelin levels in H. pylori infected subjects can be compensated by other extra gastric ghrelin producing tissues, convenient to our results. All together, further studies are needed to demonstrate the association between H. pylori infection and plasma ghrelin levels.

Hospital admissions and primary care attendances for nonulcer dyspepsia, reflux oesophagitis and peptic ulcer in Scotland 1981–2004

The aim of this study was to assess the recent time trends of oesophageal disorders, nonulcer dyspepsia, gastric and duodenal ulcer in the light of such risk factors as age, sex, deprivation and urban versus rural residence. The Scottish National Health Service provided diagnostic data on all admissions to all Scottish hospitals from 1981 to 2004 and patient visits to general practitioners (GP) from 1998 to 2004. In the last quarter of a century in Scotland, there were sevenfold increases in annual hospitalizations for dyspepsia (from 900 to 6000 per million population) and for oesophageal disorders (from 500 to 3700). Annual hospitalisations for gastric and duodenal ulcer changed from 590 to 1100 and from 1400 to 1130 per million population, respectively. The variation of hospital admissions for dyspepsia among various Scottish regions closely matched the variation of deprivation among them. GP contacts for dyspepsia (27 600 per million population) and oesophageal disorders (10,000) were common compared with relatively infrequent contacts for gastric ulcer (500) and duodenal ulcer (1200). Dyspepsia showed a rise of GP contacts with increasing scores of deprivation. This rise occurred similarly among urban and rural residents and applied to data for each individual year between 1998 until 2004. None of the other diagnoses showed any clear-cut correlation with grade of deprivation. Gastric and duodenal ulcer are relatively rare causes for hospital admission as well as outpatient physician visits. Their former predominant role in upper gastrointestinal disease has been replaced by gastro-oesophageal reflux disease and nonulcer dyspepsia, both increasing sevenfold in the last quarter of a century.

Gastrointestinal endoscopy in the dog and cat. Part 2: Lower GI tract and biopsy techniques

Evaluation of the lower gastrointestinal tract, or colonoscopy, is a safe procedure for the investigation of patients exhibiting signs of colonic disease. Signs may include dyschezia, tenesmus, constipation, chronic diarrhoea or vomiting. Patients with suspected lower gastrointestinal disease should usually first undergo routine biochemical and haematological testing and faecal analysis. A rectal examination should always be performed to identify obvious disease precluding the need for endoscopy, and to ensure that endoscopy can be performed safely. Other imaging studies commonly used in the initial investigation of the patient with upper gastrointestinal disease are less often rewarding for the diagnosis of lower gastrointestinal disease.

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.

Association between Helicobacter pylori genotypes and gastric disorders in relation to the cag pathogenicity island

Helicobacter pylori is a bacterium associated with upper gastrointestinal diseases in humans. However, only a small proportion of infected people become sick. Although several studies have tried to establish an association between known virulence markers and clinical outcomes, in many cases the results have been conflicting. The aim of this study was to investigate the importance of virulence markers to predict clinical outcome in Brazil. Mixed infections by genetically unrelated strains detected by vacA genotyping were found in 18% of the patients. The cagA and cagE genes and the vacAs1 genotype were associated with the development of peptic ulcer disease (PUD). The cagAvacAs1m1 genotype was associated with PUD and duodenal ulcer (DU). Conversely, jhp947 was not associated with DU or PUD, indicating that this gene is not a universal virulence marker. These results also show that a high proportion of the patients were simultaneously infected by cag-positive and cag-negative H. pylori types. This finding suggests the existence of a dynamic equilibrium between the loss and gain of the cag pathogenicity island, probably depending on the physiologic conditions of the patient's stomach. To the best of our knowledge, this is the first study that has documented this finding in Brazil.

Unusual upper gastrointestinal diseases associated with achalasia: laparoscopic approach

As a result of the high success rate associated with the laparoscopic approach for achalasia, surgery for the disease has become the treatment of choice in recent years. With the greater number of patients undergoing surgery, surgeons may encounter other upper gastroesophageal illnesses associated with achalasia, and these may require evaluation for simultaneous surgical treatment. This study aimed to evaluate the incidence of gastroesophageal diseases associated with achalasia, and to determine the possibility for simultaneous management using the laparoscopic approach. From January 1999 to May 2006, 81 patients were referred from the Service of Gastroenterology to the Service of General and Digestive Surgery as candidates for the surgical management of achalasia. Data for this group were recorded prospectively in laparoscopic surgery databases at the Hospital Sant Pau and the Hospital de Igualada. A total of 78 patients underwent laparoscopic Heller myotomy with gastric fundoplication. In 8 of 81 patients, nine additional gastroesophageal diseases (11.1%) were found: three cases of pseudoachalasia (3.7%), three cases of paraesophageal hiatal hernia (3.7%), two cases of esophageal diverticulum (2.5%), and one case of gastric volvulus (1.2%). Pseudoachalasia was diagnosed for three patients. The diagnosis was made preoperatively for one of these patients. For the other two patients, an adenocarcinoma arising from the gastroesophageal junction was diagnosed during the laparoscopy. In three cases, a paraesophageal hiatal hernia was found and treated by laparoscopic Heller myotomy, sac excision, hiatal closure, and posterior fundoplication. Esophageal diverticulectomy was performed for one patient. Another patient presented with an organoaxial gastric volvulus associated with achalasia, for which laparoscopic Heller myotomy, posterior fundoplication, and anterior gastropexy were performed. The median follow-up period was 39 months, with no recurrence. Despite their infrequency, several gastroesophageal diseases may be found in association with achalasia. Laparoscopic surgery may be useful for the diagnosis and/or treatment of both diseases.

The relationship between nutrition and upper gastrointestinal diseases

The relationship between nutrition and upper gastrointestinal diseases