Strategies for Helicobacter pylori eradication in patients with gastric cancer

  Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and peptic ulcer, and is closely associated with gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Currently, it is believed that the occurrence of gastric cancer is the result of multiple factors, with genetics, environment and H. pylori infection playing an important role, and H. pylori infection is the most certain risk factor for the occurrence of gastric cancer. Prospective epidemiological studies have shown that the risk of gastric cancer is 6 times higher in H.pylori-infected patients than in non-infected patients. long-term chronic infection with H.pylori in the stomach leads to long-term chronic inflammation of the gastric mucosa, from normal gastric mucosa through non-atrophic gastritis, atrophic gastritis, intestinal epithelial hyperplasia, and heterogeneous hyperplasia to gastric cancer. There is strong evidence that eradication of H. pylori can reduce the risk of gastric cancer development. A 15-year randomized, double-blind, placebo-controlled intervention study conducted by Professor You Weicheng’s team at Peking University Cancer Hospital in Linqu, Shandong Province, on 3,365 H.pylori-infected patients, showed that the incidence of gastric cancer and mortality were significantly lower in the H.pylori eradication group compared to the placebo group. In addition, a meta-analysis study found that H. pylori eradication significantly improved or reversed atrophic gastritis of the gastric sinuses, especially the gastric body, in some patients. In patients who have developed early gastric cancer, eradication of H. pylori before and after endoscopic mucosal resection (ESD) for early gastric cancer may significantly reduce the incidence of heterochronic gastric cancer and avoid recurrence after ESD for early gastric cancer.  The current consensus recommendation is to consider H.pylori eradication for gastric cancer prevention in the following cases (level of evidence: 1a-4, recommendation level: A): first-degree relatives of patients with gastric cancer; patients with gastric tumors treated with endoscopic or surgical subtotal gastrectomy; patients with gastritis at risk for gastric cancer such as severe total gastritis, gastric body-dominant gastritis, or severe atrophy; patients treated with PPI acid suppression for more than 1 year; patients with strong environmental risk factors for gastric cancer risk factors (heavy smoking, high exposure to dust, coal, quartz, cement and or working in a quarry). H.pylori-positive individuals with fear of gastric cancer.      And, H.pylori should be eradicated before precancerous lesions such as atrophy and intestinalization of the gastric mucosa occur in order to effectively prevent the development of gastric cancer. Intervention studies from the population showed that H.pylori eradication did not significantly reduce the incidence of gastric cancer after the gastric mucosa had developed atrophy, intestinalization, and atypical hyperplasia lesions, while H.pylori eradication significantly reduced the incidence of gastric cancer when the gastric mucosa was still in the superficial inflammatory stage. In a Taiwanese cohort study, 80,255 hospitalized peptic ulcer patients with H. pylori infection were treated with H. pylori eradication at early (within 1 year) and late (after 1 year) stages of infection, and were followed up for 10 years, and early H. pylori eradication was found to significantly reduce the cumulative incidence of gastric cancer (p=0.0128).  Clinically, H.pylori-related testing is required to identify H.pylori infection in patients who meet the indications for H.pylori eradication. Current testing methods are divided into invasive and non-invasive tests according to whether gastric mucosal biopsies need to be clamped by gastroscopy. Invasive tests include rapid urease test, pathological tissue section staining, bacterial culture, and genetic testing methods; non-invasive tests include 13C or 14C urea breath test, H.pylori stool antigen test, and H.pylori serum antibody detection. To avoid false negatives in H.pylori infection testing, the test should be performed only after 2 weeks of discontinuation of PPI and 4 weeks of discontinuation of antibiotics, bismuth, and herbal medicines with antibacterial effects. Patients with early gastric cancer after ESD can be routinely tested for H.pylori infection, while in patients with residual stomach after major gastrectomy for mid- to late-stage gastric cancer, the large amount of bile in the stomach can inhibit H.pylori, resulting in false-negative tests. It is recommended to take gastric mucosal biopsy tissue for rapid urease test in both fundus and body clamp; the use of breath test for H.pylori infection is not recommended due to rapid urea emptying in the remnant stomach. For patients with residual stomach, rapid urease test is better than breath test, while histological detection method is better than urease based detection; serological detection method is not affected by changes in gastric environment, but it is still difficult to diagnose presenting infection; serological + histological method or HpSA is recommended, which has better sensitivity and specificity; multiple methods can be used in combination in the clinic, which can improve the accuracy of detection and avoid False negatives of H.pylori detection in postoperative patients with gastric cancer.  Current H.pylori eradication regimens include standard triple therapy, bismuth quadruple therapy, as well as sequential therapy recommended by the European Maastricht IV consensus, antibiotic-concomitant therapy without bismuth, and triple therapy with levofloxacin. However, due to the increasing rate of antibiotic resistance of H. pylori, the eradication rate of H. pylori by standard triple therapy in China has been very low, and the eradication rate of intention-to-treat (ITT) is only about 63.5%, which is no longer suitable as the first-line therapy. In China, sequential therapy, antibiotic-concomitant therapy and levofloxacin-containing triple therapy may lack evidence-based medical evidence or have poor eradication rates. Therefore, our fourth H. pylori consensus recommends standard doses of proton pump inhibitors combined with bismuth plus two antibiotics for the eradication of H. pylori; for those who have contraindications to bismuth or when H. pylori resistance rates are still confirmed to be low The standard triplet regimen, sequential therapy and antibiotic concomitant therapy without bismuth are available for 10-14 days, with an interval of 2-3 months between initial and remedial therapy. The available antibiotics include amoxicillin, clarithromycin, metronidazole, tinidazole, furazolidone, tetracycline, levofloxacin, and moxifloxacin. Different combinations of antibiotics can be combined to form different eradication protocols. Among them, amoxicillin, tetracycline and furazolidone are sensitive antibiotics, while metronidazole, clarithromycin and levofloxacin are resistant antibiotics. The individualization of eradication treatment is also emphasized. Before eradication treatment, patients should be carefully asked about the history of previous antibiotic application (clarithromycin, levofloxacin, etc.), the history of drug allergy and potential adverse reactions, to determine whether concomitant diseases affect drug metabolism and excretion, and the possibility of increased adverse reactions. For patients of advanced age, the adverse reactions of eradication treatment drugs may be increased, while gastric cancer prevention-based The benefit of eradication therapy may be reduced in patients with advanced age. Patients should be informed of the potential adverse effects of eradication therapy prior to treatment in order to obtain better compliance. The effect of H.pylori eradication therapy on the prevention of gastric cancer recurrence is similar in patients with gastric cancer treated with H.pylori before or after surgery; the bile in the residual stomach and the higher pH in the stomach facilitate the success of H.pylori eradication therapy.  In conclusion, H.pylori infection is a risk factor for gastric cancer development; eradication of H.pylori reduces the risk of gastric cancer development, reverses some atrophic gastritis, and reduces the occurrence of heterochronic gastric cancer after gastric cancer surgery. Clinically, for patients after radical gastric cancer surgery, appropriate tests should be selected to diagnose H. pylori infection. The quadruple therapy of proton pump inhibitor combined with bismuth is the current recommended regimen for H.pylori eradication, and the individualization of the regimen should be adhered to during clinical consultation and treatment to improve the first eradication rate.