幽门螺杆菌与胃黏膜相关淋巴瘤相关性研究

目的研究幽门螺杆菌(H.pylori)与胃黏膜相关淋巴瘤相关性。方法通过胃镜和相关辅助检查,对24例胃黏膜相关淋巴瘤病人胃内幽门螺杆菌进行动态观察。结果24例胃黏膜相关淋巴瘤病人中,18例出现H.pylori感染(75%);治疗后H.pylori感染例数减少(6/24,25%);1年后H.pylori病人感染又增加(11/24,46%)。结论抗H.pylori及胃黏膜相关淋巴瘤常规治疗方法有效,但易反复,可考虑辅以微生态调节剂治疗。     

Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori

Background and Aims: The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. Methods: The subjects were 18 early‐stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. Results: The average diameter of gastric cancer was smaller and Ki‐67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Conclusion: Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer.     

Serum antibodies to Helicobacter pylori and its heat-shock protein 60 correlate with the response of gastric mucosa-associated lymphoid tissue lymphoma to eradication of H. pylori

Background and aims. Eradication of Helicobacter pylori leads to regression of mucosa‐associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori‐recombinant heat‐shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy. Methods. Serum samples were obtained from 33 patients with H. pylori‐positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti‐H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain. Results. Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre‐treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p = .0011 and .035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80–0.99), endoscopic appearance (0.053, 0.004–0.65), titers of anti‐H. pylori antibodies (67.6, 2.5–1800), and titers of anti‐rHSP60 antibody (6.4, 1.2–36) were identified as significantly associated factors with the outcome of MALT lymphoma. Conclusions. Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori.     

Anti‐Helicobacter pylori therapy in localized gastric mucosa‐associated lymphoid tissue lymphoma: A prospective,nationwide, multicenter study in Japan

Background

Helicobacter pylori eradication therapy was approved in Japan for the first‐line, standard treatment of H. pylori‐positive gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small‐scale single‐center studies have been reported, a prospective, large‐scale, nationwide, multicenter study has not been reported from Japan.

Materials and Methods

We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole‐based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice‐based clinical trial. A total of 108 H. pylori‐positive patients with stage I/II₁ gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS).

Results

CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0‐44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4‐53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow‐up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma.

Conclusions

Rabeprazole‐based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice‐based, multicenter study.     

Helicobacter pylori recurrence in developed and developing countries: meta-analysis of 13C-urea breath test follow-up after eradication

Objective: Recurrence of Helicobacter pylori infection after eradication is rare in developed countries and more frequent in developing countries. Most recurrent cases are attributed to recrudescence (recolonization of the same strain within 12 months) rather than to reinfection (colonization with a new strain after more than 12 months). The aim of the study was to analyze recurrence rates in developed and developing countries and to deduce the relative roles of recrudescence and reinfection. Methods: The PubMed database was searched up to January 31, 2007 using the keywords “Helicobacter pylori” or “H. pylori” and “recurrence” or “recrudescence,” or “reinfection.” Only prospective case studies in adults that used the ¹³C‐urea breath test (¹³CUBT) were included. Meta‐analyses were performed with statdirect Statistical software, version 2.6.1, StatsDirect Ltd, Chesire, UK. Results: The literature search yielded 10 studies of H. pylori recurrence in developed countries (3014 patients followed for 24–60 months) and 7 studies in developing countries (2071 patients followed for 12–60 months). The calculated annual recurrence rates were 2.67% and 13.00%, respectively. Nested meta‐analysis of cases with a longer follow‐up after eradication revealed an annual recurrence rate of 1.45% (RR 0.54) in developed countries and 12.00% (RR 0.92) in developing countries. Conclusions: The similarity of the annual recurrence rates during the first year after eradication and the annual recurrence rates in the second year after successful eradication in developing countries supports reinfection as the main cause in the second period. Therefore, a different approach for follow‐up of H. pylori eradication may be needed between developed and developing countries.     

Modulation of lymphocyte proliferation induced by gastric MALT lymphoma-associated Helicobacter pylori strains

Background: Helicobacter pylori infection leads to different chronic diseases, suggesting that this bacterium can evade the host immune defense system. The ability to control lymphocyte proliferation may be a mechanism leading to the development of gastric pathologies. Our aim was to characterize the effects of mucosa‐associated lymphoid tissue (MALT) associated H. pylori strains on lymphocyte proliferation. Materials and methods: We measured the in vitro proliferation of human lymphocytes originally from blood or tonsil samples in the presence or absence of viable bacteria or lysates. Results: We showed that MALT lymphoma‐associated strains are not likely to be directly responsible for anarchical B‐cell proliferation in vitro. On the other hand, proliferation of prestimulated T lymphocytes was abolished in vitro by the presence of all H. pylori strains, whether associated with MALT lymphoma or not. Conclusion: Inhibition of T‐cell proliferation may be of major importance in the gastric colonization and in the persistence of the infection. Furthermore, this inhibition may favor anarchical B‐cell proliferation in vivo and predispose the host to gastric MALT lymphoma, whereas MALT‐associated H. pylori strains do not appear to possess a specific capability to directly stimulate B‐lymphocyte proliferation.     

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis

Background

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.

Materials and Methods

PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.

Results

Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81–0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17–1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69–0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30–2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15–1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37–2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47–1.70), Hp eradication had no advantage compared to placebo or no treatment.

Conclusions

Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.     

Does Helicobacter pylori eradication affect symptoms in nonulcer dyspepsia: a 5-year follow-up study

The role of Helicobacter pylori infection in nonulcer dyspepsia remains controversial. To date studies exploring the effect of H. pylori eradication on symptoms have reported conflicting results. Randomised control trials employing validated outcome measures have also been difficult to interpret because of several important issues such as the large placebo response seen in patients with nonulcer dyspepsia and both the natural variability in symptoms and symptom severity with time. The association of symptom improvement with resolution of gastritis has meant that the length of follow up employed in most studies has been insufficient. We report the findings of a randomised placebo controlled trial (n = 100), using a validated symptom questionnaire and 5 year follow up to determine the effect of H. pylori eradication on symptoms in nonulcer dyspepsia. In all 64 that were reviewed at 5 years there was a significant difference between patients who were H. pylori negative and those who remained positive with regard to complete symptom resolution, consumption of relevant medications and peptic ulcer disease development, in favour of active treatment. There was a trend for gradual symptom improvement over time irrespective of H. pylori status, which may reflect the natural history of this condition. For those who remained symptomatic at 5 years, there was no difference in symptom severity based on H. pylori status. The findings of this study support the use of H. pylori eradication in symptomatic patients with nonulcer dyspepsia both to induce symptom resolution and to prevent disease progression.     

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

Long-term follow-up after eradication of Helicobacter pylori with omeprazole, clarithromycin, and tinidazole (OCT regimen) in a Japanese population

BACKGROUND: The long-term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re-infection and ulcer relapse after H. pylori eradication. MATERIALS AND METHODS: A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C-urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy. RESULTS: Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori-positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re-infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years. CONCLUSION: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re-infection rate in this population.     

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third‐line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin‐metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI‐B‐T‐M) three times a day (tid) for 1 week. In the case of treatment failure with this second‐line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI‐B‐T‐F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI‐B‐T‐M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI‐B‐T‐F. Final cure of H. pylori with PPI‐B‐T‐F was achieved in 9/10 patients (90%) nonresponsive to PPI‐B‐T‐M. Conclusions. In the presence of metronidazole resistance, PPI‐B‐T‐M as a recommended second‐line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second‐line quadruple therapy may be best suited in case of a metronidazole‐free first line‐regimen (e.g. PPI‐clarithromycin‐amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI‐B‐T‐F combination does not have a cross‐resistance potential to metronidazole and is a promising salvage option after a failed PPI‐B‐T‐M regimen.