Israel Medical Association Journal

Background: The trefoils factor family is a relatively new family of peptides. Their abundant expression in the epithelial cells of the gastrointestinal tract in the normal physiological state and in various ulcerative conditions suggests an important role in mucosal defense and repair. Infection with Helicobacter pylori interferes with normal mucosal activity.

Objectives: To investigate whether H. pylori infection alters the expression of trefoils TFF1[1] and TFF2 in the gastric mucosa of patients with H. pylori-associated chronic active gastritis, positive or negative for the CagA strain.

Methods: During investigation for dyspepsia, gastric biopsies and blood samples were obtained from patients who underwent upper gastrointestinal endoscopy. Rapid urease testing, histology for determination of H. pylori-associated CAG[2] and Western analysis for TFF1 and TFF2 expression with antisera were performed. CagA state was determined using a commercial kit.

Results: TFF2 expression was significantly reduced in both groups of patients with H. pylori-associated CAG compared to healthy patients without H. pylori infection, particularly in CagA-positive patients. TFF1 expression showed a tendency of reduction (not significant) in this group only.

Conclusions: These results suggest that H. pylori-associated CAG has a deleterious effect on the expression of TFF2 in the gastric antrum. This reduced expression may contribute to the damage induced to the gastric mucosa by H. pylori.

Background: The ¹³C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibodies titer.

Objectives: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by ¹³C-UBT[1] in our central laboratory and to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success.

Methods: ¹³C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy.

Results: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI[2] therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01).

Conclusion: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as described in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Background: Current treatment for the eradication of Helicobacter pylori in patients with peptic disease is based on the combination of antibiotic and anti-acid regimens. Multiple combinations have been investigated, however no consensus has been reached regarding the optimal duration and medica­tions.

Objectives: To assess the efficacy of two treatment regimens in patients with peptic ulcer disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal culture in patients failing previous treatment.

Methods: Ninety patients with established peptic ulcer and NUD (with previously proven ulcer) were randomly assigned to receive either bismuth-subcitrate, amoxycillin and metrnida­zole (8AM) or lansoprasole, clarithromycine and metronida­zole (LCM) for 7 days. Patients with active peptic disease were treated with ranitidine 300 mg/day for an additional month.

Results: Eradication failed in 8 of the 42 patients in the 8AM group and in 2 of the 43 patients in the LCM group, as determined by the ¹³C urea breath test or rapid urease test (19% vs. 5%, respectively, P=0.05). Five of these 10 patients were randomly assigned to treatment with lansoprazole, amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the other 5 patients were assigned to treatment with lansoprazole and two antibacterial agents chosen according to a susceptibility test. Eradication of H. pylon was confirmed by the ‘³C urea breath test. The same protocol (LAC) was used in all patients in the first group and in four of the five patients in the second group. The culture results did not influence the treatment protocol employed.

Conclusions: Combination therapy based on proton pump inhibitor and two antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal culture testing for sensitivity of H. pylon to antibiotics is probably unnecessary before the initiation of therapy for patients with eradication failure.

Objective: To investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients.

Patients and Methods: The study group comprised 596 consecutive H. pylori-positive dyspeptic patients (334 males and 262 females, mean age 50.6, range 12--81 years). Following upper gastrointestinal endoscopy, patients were subdivided by diagnosis as follows: Non-ulcer patient group (n=312: gastritis 193, duodenitis 119), gastric ulcer (n=19), and duodenal ulcer (n=265). H. pylori infection was confirmed by histology and/or rapid urease test. In addition, 244 patients had a positive 14C-urea breath test prior to antimicrobial treatment. The patients' medical history and smoking habits were obtained using a detailed questionnaire completed by the patients and their referring physicians.

Results: There were 337 non-smoking patients, 148 current smokers and 111 past smokers. Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3273 units) than in past smokers (mean 320.8199) or current-smokers (mean 229.9162) (P0.05). Logistic regression analysis revealed that male gender, current smoking, and immigration from developing countries were all significant independent risks for developing duodenal ulcer, while only past smoking was associated with a higher rate of upper gastrointestinal bleeding in the past.

Conclusions: In H. pylori-positive dyspeptic patients, current smoking as well as male gender and immigration from developing countries are associated with an increased risk for duodenal ulcer. This effect does not seem to be related to the bacterial density or increased urease activity of H. pylori organisms.

Background: Recurrent abdominal pain is a common pediatric diagnostic problem.  Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology.

Objectives: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP.

Patients and Methods: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months.

Results: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P<0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P<0.01 between the H. pylori-associated gastritis and each of the other groups).

Conclusions: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

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RAP = recurrent abdominal pain

Background: Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa.

Objectives: To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease.

Methods: The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9.

Results: H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P=0.05). A significant correlation was found between CA 19-9 (γ=0.3432, n=49, P=0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer.

Conclusions: The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.