Role of Helicobacter pylori infection on upper gastrointestinal bleeding in the elderly. A case-control study

Nonsteroidal antiinflammatory drug (NSAID) use is known to be associated with a high incidence of upper gastrointestinal tract bleeding in the elderly. The increased prevalence of Helicobacter pylori (HP) infection, which also occurs with age, suggests that an interaction between NSAID use and HP infection may explain the higher incidence of ulcer complications in the elderly. The aim of the present study was to determine if a relationship exists between HP infection and NSAID use in elderly patients with upper gastrointestinal bleeding. This was a case-control study on 146 elderly patients (73/group). The bleeding group consisted of 37 males and 36 females (mean age 80.4 years, range 70-96) with symptoms (hematemesis, melena, anemia with loss of more than 3 g hemoglobin), and endoscopic stigmata of bleeding. The control group consisted of 73 age- and sex-matched patients with the same endoscopic diagnosis but with no endoscopic stigmata of bleeding. NSAID use was evaluated by interview at the time of endoscopy, and HP infection was confirmed in all cases by histology and the rapid urease test. Statistical analyses were performed using the chi-square test and logistic regression. In both groups, 46.57% of patients were affected with gastric ulcer, 36.98% with duodenal ulcer, and 16.43% with erosive gastritis. The bleeding group had a significantly higher percentage of NSAID users (53.42% vs 19.17%, P < 0.0001) and a lower percentage of HP-positive patients (47.94% vs 72.60%, P = 0.004). The NSAID use pattern was as follows: occasional users (sporadic, as needed during the previous week): 53.8% of bleeding cases and 50% of controls; acute users (continuous therapy for less than one month): 17.9% of bleeding cases and 28.5% of controls; and chronic users (continuous therapy for more than one month): 28.2% of bleeding cases and 21.4% of controls. The logistic regression demonstrated that NSAID use was significantly related to an increase risk of bleeding both in gastric (odds ratio: 4.98, 95% CI: 1.83-13.6) and duodenal ulcer patients (odds ratio: 10.2, 95% CI: 2.25-46.7) while HP-positivity presented a significant inverse relationship with bleeding only in subjects with gastric lesions (odds ratio: 0.20, 95% CI: 0.07-0.55). NSAID use and HP infection were also shown to be independent, unrelated factors, with the overall risk of bleeding in HP-positive NSAID users identified to be significantly less than in HP-negative NSAID users. In conclusion, in elderly patients: (1) NSAID use increases the risk of upper gastrointestinal bleeding while HP infection was associated with a low risk for gastric bleeding; and (2) the two factors are independent variables, therefore the HP-positive NSAID user has a lower risk than the HP-negative NSAID user

The long-term clinical outcome of elderly patients with Helicobacter pylori-associated peptic ulcer disease

The objective of this study was to evaluate the long-term efficacy of Helicobacter pylori (HP) eradication treatment in elderly patients with HP-associated peptic ulcer. A total of 56 subjects, 25 affected with gastric ulcer (GU, 9 males, 16 females, mean age 77.8 years, range 67-93) and 31 with duodenal ulcer (DU, 19 males, 12 females, mean age 76.5 years, range 65-87) were confirmed to be HP-positive by gastric histology and the rapid urease test. All patients were then consecutively treated with omeprazole for 4 weeks plus one or two antibiotics for 1 week as anti-HP treatment. Clinical checkups were then performed every 3 months for 1 year for the evaluation of symptoms and clinical recurrences. Endoscopy with gastric biopsies was repeated after 1, 3 and 12 months for the evaluation of ulcer healing, HP infection and chronic gastritis activity. Statistical analysis was performed by means of the Student t test for unpaired data, the Fisher exact test (two-tailed), and the McNemar Ï\u872 test. After 4 weeks of treatment, endoscopy confirmed healing of the ulcer in all patients, regardless of the treatment used to cure HP infection. Two months after the end of therapy, a total of 44 patients were HP-negative and 12 patients were still HP-positive. During the 1-year follow-up period 1/44 (2.2%) of the HP-eradicated patients and 5/12 (41.6%) of the still HP-positive patients suffered relapses (p = 0.001): the difference between the two groups remained statistically significant when patients were divided into the subgroups, GU (p = 0.01) and DU (p = 0.04). Two months after the end of therapy, there was still a significant reduction of symptoms both in HP-eradicated (p < 0.0000) and in HP-positive (p = 0.002) patients. After 1 year, however, there was a significantly decreased symptomatology only in HP-eradicated subjects (p < 0.0000) and not in patients still HP-positive. After both 2 months and 1 year of follow-up, chronic gastritis activity demonstrated a significant improvement only in HP-eradicated patients (p = 0.0000). In conclusion, the eradication of HP infection significantly improved the long-term clinical outcome of peptic ulcer disease in the elderly, reducing the recurrences of GU and DU, the patient's symptomatology and the histological signs of chronic gastritis activity. The cure of HP infection is, therefore, strongly recommended in elderly patients with HP-associated peptic ulcer disease

Cytotoxin-Associated Gene A-Positive Helicobacter pylori infection in the Elderly: Association with gastric atrophy and intestinal metaplasia

To evaluate if the infection with swains of cytotoxin-associated gene A (CagA)-positive Helicobacter pylori is associated with either peptic ulcer and gastric atrophy or intestinal metaplasia in the elderly, we studied 71 H. pylori-positive patients older than 62 years old (34 men, 37 women; mean age, 77.5 years; range, 62-89 years) affected with gastric ulcer (GU) (n = 10), duodenal ulcer (DU) n = 22), or chronic gastritis (CG) (n = 39). H. pylori infection was documented by means of gastric histology, rapid urease test, and polymerase chain reaction (PCR) assay performed on gastric biopsies using two sets of primers: one for the ureC gene specific for H. pylori, and the second specific for the CagA gene. H. pylori-CagA positivity was significantly more common in patients with GU (9 of 10, 90%) than with DU (11 of 22, 50%; p < 0.05) or CG (17 of 39, 43.5%; p = 0.01). Gastric atrophy and intestinal metaplasia were significantly more common in CagA-positive patients than in CagA-negative patients (gastric atrophy: 40.54% vs 11.76, p = 0.007; intestinal metaplasia: 40.54% vs 14.70%, p = 0.01). No difference in prevalence of gastric atrophy and intestinal metaplasia was found in patients divided according to pathology (GU, DU, or CG). Logistic regression demonstrated that gastric atrophy and intestinal metaplasia were independent factors significantly associated with CagA-positivity (gastric atrophy: odds ratio = 4.53, 95% confidence interval 1.25-16.4; intestinal metaplasia: odds ratio = 3.44, 95% confidence interval 1.01-11.7). Our findings help to confirm the hypothesis that an infection with CagA-positive H. pylori strains may be catalytic in inducing gastric changes which can evolve into malignancies

Barrett's esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian Registry (EBRA)

OBJECTIVE: To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barrett's esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. BACKGROUND: BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. METHODS: In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. RESULTS: HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2-4); median follow-up = 44.6 [IQR: 24.7-60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51-68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9-50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63-21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22-11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03-1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. CONCLUSIONS: These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments