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.     

Previous Helicobacter pylori infection–induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication

Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false‐negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection–induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton‐pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%‐0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%‐0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection–induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high‐risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high‐risk subgroup of this understudied population is especially important.     

Macrolide use in the previous years is associated with failure to eradicate Helicobacter pylori with clarithromycin‐containing regimens

Background

There is some evidence that prior use of macrolide antibiotics is a useful predictor of the likelihood of standard triple therapy failure in Helicobacter pylori eradication. In this study, we have evaluated whether previous intake of macrolides correlates with failure to eradicate H. pylori using two different first‐line clarithromycin‐containing regimens.

Materials and Methods

Retrospective study of 212 patients with H. pylori infection treated with one of two first‐line clarithromycin‐containing regimens: 108 patients treated with triple therapy for 10 days and 104 patients treated with concomitant therapy for 10 days. The intake of macrolides (clarithromycin, azithromycin, and other macrolides) prior to the eradication therapy was obtained from the electronic medical record, which contains information regarding all the medication prescribed to the patients since the year 2004.

Results

One hundred of 212 patients (47.2%) had received at least one treatment with macrolides during the years prior to the eradication therapy. H. pylori eradication rates were significantly lower in patients with previous use compared to patients without previous use of macrolides, both with triple therapy (60.8% vs 92.9%; P < .0001) and with concomitant therapy (85.7% vs 98.2%; P = .024).

Conclusions

Previous use of macrolides correlates with a low H. pylori eradication rate with triple and concomitant clarithromycin‐containing regimens. In addition, our study shows that in patients without previous use of macrolides, triple therapy achieves per‐protocol eradication rates over 90%.     

Review: Clinical Management of Helicobacter pylori Infection in China

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.     

An increasing trend of gastric cancer deaths and inadequate preventive measures in elderly adults

Background

Japan became the world's first country to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system in February 2013. Thereafter, H. pylori eradication dramatically increased and gastric cancer deaths began to decrease in Japan. However, the details of gastric cancer deaths and its prevention in the very elderly have not been fully elucidated.

Methods

We analyzed the temporal trend of gastric cancer deaths referencing data from Ministry of Health, Labour and Welfare reports and “Cancer Statistics in Japan–2021” and assessed the numbers of H. pylori test and gastric cancer screening using a national database and a report of cancer screening in Shimane Prefecture, respectively.

Results

Although gastric cancer deaths in total population have clearly decreased since 2013, those in people aged 80 years and older are still increasing. People aged 80 years and older represent 9% of the total population and accounted for half of all gastric cancer deaths in 2020. The numbers of H. pylori eradication and gastric cancer screening in people aged 80 years and older were 25% and 25% of those in other generations, respectively.

Conclusion

In spite of a dramatic increase in H. pylori eradication and a clear decrease in gastric cancer deaths in Japan, gastric cancer deaths in people aged 80 years and older are increasing. This might be due to fewer H. pylori eradication in the elderly than in other generations, indicating the difficulty of gastric cancer prevention in the very elderly.     

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.     

H. pylori predictors and outcomes among adults undergoing upper endoscopy at a Jamaican teaching hospital: A cross-sectional study

Background

Recent data on the prevalence of H. pylori infection in Jamaica are lacking. It is postulated that there has been a decline in the prevalence of H. pylori infection and its associated complications. We determined sociodemographic characteristics, prevalence of H. pylori infection and clinical outcomes among adults undergoing esophagogastroduodenoscopy (EGD) and histology at the University Hospital of the West Indies (UHWI) between May 2018 and December 2020.

Materials and methods

A cross-sectional study of patients (≥18 years old), who underwent EGD and histological evaluation for H. pylori infection, was conducted. Associations of H. pylori positivity and gastric cancer with sociodemographic/clinical variables and endoscopic findings were determined by stepwise logistic regression using backward selection. Unadjusted and adjusted odds ratios with related 95% confidence intervals (Cis) were calculated for H. pylori positivity and gastric cancer status.

Results

There were 323 participants (mean age 58.6 ± 17.8 years, 54.2% females). H. pylori prevalence was 22.2% (n = 70 of 315), 5.6% had gastric neoplasia (GN), 15.5% gastric atrophy, 11.4% intestinal metaplasia and 3.7% dysplasia on histology. Mucositis (64.5%), gastric ulcer (14.9%), and duodenal ulcer (13.9%) were the most common endoscopic findings. Participants with peptic ulcer disease (PUD) (unOR = 4.0; p = .017), gastric cancer (unOR = 9.5; p = .003), gastric atrophy (unOR = 12.8; p < .001), and intestinal metaplasia (unOR = 5.0; p < .001) had a significantly higher odds of being H. pylori positive, but after multivariable analyses only gastric atrophy remained significant (aOR = 27.3; p < .001). Participants with mucositis had a significantly lower odds of gastric cancer (unOR 0.1; p = .035) while participants with dysplasia had significantly higher odds (unOR 8.0; p = .042), but these were no longer significant after multivariable analyses (aOR = 0.2; p = .156 and aOR = 18.9; p = .070, respectively).

Conclusions

Histology based prevalence of H. pylori infection is lower than previously reported in Jamaica. Gastric atrophy is a significant predictor of H. pylori positivity.     

The role of abdominal CT scan as follow-up after complete remission with successful Helicobacter pylori eradication in patients with H. pylori-positive stage I(E1) gastric MALT lymphoma

Background: Eradication of Helicobacter pylori with antibiotics is the established initial treatment of patients with localized gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. However, there are few reports on follow‐up modalities to identify sustained remission in patients who achieve complete remission (CR). We therefore investigated the role of abdominal computed tomography (CT) as follow‐up after CR with H. pylori eradication. Patients and Methods: We retrospectively analyzed 122 patients with H. pylori‐positive stage I_E1 gastric MALT lymphoma who achieved CR with successful H. pylori eradication. Results: The median follow‐up after CR was 35 months (range 3–140months). At a median of 17 months (range 12–21 months) after CR, 7 of 122 patients (5.7%) experienced lymphoma recurrence, all cases of which were confined to the gastric mucosa and were detectable only by endoscopy with multiple biopsies. At the time of recurrence, four of seven patients showed re‐infection by H. pylori. Eradication therapy was successful in these patients, resulting in both bacterial eradication and tumor regression. Three patients who experienced histologic recurrence without H. pylori re‐infection were observed by a watch and wait strategy and again achieved CR. Conclusions: None of the patients with H. pylori‐positive stage I_E1 gastric MALT lymphoma who experienced tumor recurrence after CR with successful H. pylori eradication showed recurrence at extragastric sites, including lymph nodes without gastric mucosal lesion. These findings indicate that endoscopic biopsies without abdominal CT scans are sufficient to detect recurrence in these patients.     

Helicobacter pylori antimicrobial resistance in a pediatric population

Background

The increasing prevalence of Helicobacter pylori (H. pylori) antimicrobial resistance, primarily for clarithromycin decreases the success of treatment. The aim of this study is to determine the local pattern of first‐line antimicrobials resistance and the eradication rate.

Material and Methods

Prospective cohort study of H. pylori infected patients (positive histological or cultural exams) treated at Centro Materno‐Infantil do Norte from January of 2013 to October of 2017. Susceptibility to 4 antibiotics: amoxicilin, metronidazole, clarithromycin, and levofloxacin were analyzed by E‐test (phenotypic resistance). The E‐test was chosen because it is simple and cost‐effective for routine susceptibility testing. Point mutations that confer clarithromycin resistance were surveyed (genotypic resistance). Eradication of H. pylori infection was defined by a negative urea breath test or fecal antigen 6‐8 weeks after the end of treatment.

Results

Of a total of 74 H. pylori infected patients, 16 were excluded because they had previous H. pylori treatment or severe systemic disease. Median age of infection cases was 15 years (3‐17 years). Eradication regimen used in all patients combined the use of 3 antibiotics (amoxicillin and metronidazole or clarithromycin) and proton pump inibhitor for 14 days and was tailored according antimicrobial susceptibility. 79.5% of the patients completed the treatment. The resistance rate for metronidazole and clarithromycin was 3.3% and 23.3%, respectively. There was no resistance for amoxicilin and levofloxacin. The rate of genotypic resistance to clarithromycin was 37.2%. The eradication rate was 97.8%.

Conclusions

The authors found a high resistance rate of H. pylori for clarithromycin in this northern portuguese pediatric center. This factor should determine a change in local current treatment, contraindicating the use of clarithromycin as a first‐line treatment for H. pylori infection in children. The high eradication rate maybe explained for the eradication treatment tailored according antimicrobial susceptibility.     

Review: Gastric cancer—Clinical aspects

Gastric cancer (GC) was responsible for over 1 000 000 new cases in 2018 and an estimated 783 000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non‐cardia GC, were stable or increasing among persons aged <50 years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10 years before. Based on the results of a 16‐year endoscopy‐based follow‐up eradication trial, patients with incomplete‐type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first‐line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second‐line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1 months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18‐ARHGAP26/6 fusion was associated with signet‐ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine‐based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future.     

The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach

Background

Helicobacter pylori is unevenly distributed in hypochlorhydric environments. The study aim was to elucidate the risk factors for a negative Giemsa staining finding in seropositive subjects by measuring the secretory ability of the stomach.

Methods

Subjects aged over 18 years were included consecutively after endoscopic biopsy at gastric lesions with color or structural changes. Blood was sampled for the serum pepsinogen (PG) assay and H. pylori serology test. After excluding the subjects with past H. pylori eradication, the risk factors for a negative Giemsa staining finding in seropositive subjects were analyzed.

Results

Among 872 included subjects, a discrepancy between the serum anti‐H. pylori IgG and Giemsa staining findings was found in 158 (18.1%) subjects, including 145 Giemsa‐negative, seropositive subjects. Gastric adenocarcinoma/adenoma (OR = 11.090, 95% CI = 3.490‐35.236) and low serum PG II level (OR = 0.931, 95% CI = 0.899‐0.963) were the independent risk factors for a negative Giemsa staining finding in seropositive subjects. The cutoff value of serum PG II level was 7.45 ng/mL (area under curve [AUC] = 0.904, 95% CI = 0.881‐0.927). Follow‐up studies of Giemsa staining at different sites of the stomach revealed that 75% of the Giemsa‐negative seropositive subjects with adenocarcinoma are positive, whereas none of those with low serum PG II level of <7.45 ng/mL revealed positive findings.

Conclusions

The risk of a negative Giemsa staining finding in seropositive subjects is increased in gastric adenocarcinoma/adenoma specimens and in subjects with a diminished gastric secretory ability with low serum PG II level of <7.45 ng/mL. A false‐negative Giemsa staining finding is common in subjects with adenocarcinoma, and therefore, additional biopsies at different sites should be performed in these subjects.     

Antibiotics resistance of Helicobacter pylori in children with upper gastrointestinal symptoms in Hangzhou,China

Background

The decreasing eradication rate of Helicobacter pylori is mainly because of the progressive increase in its resistance to antibiotics. Studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to investigate the resistance rates and patterns of H. pylori strains isolated from children.

Materials and Methods

Gastric mucosa biopsy samples obtained from children who had undergone upper gastrointestinal endoscopy were cultured for H. pylori, and susceptibility to six antibiotics (clarithromycin, amoxicillin, gentamicin, furazolidone, metronidazole, and levofloxacin) was tested from 2012‐2014.

Results

A total of 545 H. pylori strains were isolated from 1390 children recruited. The total resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin were 20.6%, 68.8%, and 9.0%, respectively. No resistance to amoxicillin, gentamicin, and furazolidone was detected. 56.1% strains were single resistance, 19.6% were resistant to more than one antibiotic, 16.7% for double resistance, and 2.9% for triple resistance in 413 strains against any antibiotic. And the H. pylori resistance rate increased significantly from 2012‐2014. There was no significant difference in the resistance rates to clarithromycin, metronidazole, and levofloxacin between different gender, age groups, and patients with peptic ulcer diseases or nonulcer diseases.

Conclusions

Antibiotic resistance was indicated in H. pylori strains isolated from children in Hangzhou, and it increased significantly during the 3 years. Our data strongly support current guidelines, which recommend antibiotic susceptibility tests prior to eradication therapy.     

Furazolidone‐containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China

Background

The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection.

Methods

A national, multicenter, open‐label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone‐containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the ¹³C urea breath test at least 4 weeks after treatment completion.

Results

Overall, according to intention‐to‐treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%‐93.2%) and 83.6% (95% CI, 76.3%‐90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%‐89.8%) and 77.6% (95% CI, 69.4%‐85.8%), respectively. According to per‐protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%‐99.1%) and 90.8% (95% CI, 85.1%‐96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%‐96.3%) and 85.1% (95% CI, 78.2%‐92.1%), respectively. The overall prevalence of side effects was 8.1%.

Conclusions

Furazolidone‐containing therapies, particularly the tested 10‐day quadruple therapy, exhibited satisfactory efficacy and safety. This 10‐day quadruple therapy represents a promising initial treatment strategy for Chinese patients.     

Analysis of key genes and signaling pathways involved in Helicobacter pylori‐associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Background

Helicobacter pylori (H. pylori) infection is associated with the development of gastric cancer, although the mechanism is unclear. Herein, this study aimed to clarify the key genes and signaling pathways involved in H. pylori pathogenesis based on The Cancer Genome Atlas (TCGA) database and RNA sequencing analysis.

Materials and Methods

Forty‐nine gastric cancer samples (16 with H. pylori and 33 without H. pylori) and 35 cancer‐adjacent normal samples from TCGA database were analyzed by bioinformatics. The differentially expressed genes between H. pylori‐positive and H. pylori‐negative patients were verified in 18 gastric cancer (GC) samples (9 with H. pylori and 9 without H. pylori), which were analyzed using RNA sequencing. Survival analysis was carried out to explore associations between the differentially expressed genes and prognosis. Bioinformatics analysis was performed to determine the signaling pathways associated with H. pylori.

Results

The baseline level of clinical features from TCGA database and RNA sequencing showed no differences between the H. pylori‐positive and H. pylori‐negative GC groups (P > 0.05). TP53 was shown to be upregulated in the H. pylori‐positive group in both TCGA database and RNA sequencing data, which also showed higher expression in the GC tissues than in adjacent normal tissues (P < 0.05). CCDC151, CHRNB2, GMPR2, HDGFRP2, and VSTM2L were shown to be downregulated in the H. pylori‐positive group by both TCGA database and RNA sequencing, which also showed lower expression in the GC tissues than in adjacent normal tissues (P < 0.05). GC patients with low expression levels of HDGFRP2 had a poor prognosis (P < 0.05). Thirty‐three signaling pathways and 10 biological processes were found to be positively associated with H. pylori infection (P < 0.05, FDR < 0.05).

Conclusions

These results indicate that some genes (TP53, CCDC151, CHRNB2, GMPR2, HDGFRP2, VSTM2L) and previously unidentified signaling pathways (eg, the Hippo signaling pathway) might play an important role in H. pylori‐associated GC.     

Review: Prevention and management of gastric cancer

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.     

Helicobacter pylori Eradication Therapy May Facilitate Gastric Ulcer Healing After Endoscopic Mucosal Resection: A Prospective Randomized Study

Background and Aim: It remains unclear whether Helicobacter pylori eradication therapy affects the healing rate of iatrogenic ulcers following endoscopic mucosal resection (EMR) for gastric tumors. The aim of our study was to prospectively evaluate the effect of H. pylori eradication therapy on gastric ulcer healing after EMR. Methods: After EMR, patients were randomly assigned to either the H. pylori eradication group (Hp group) (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg, twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were compared between the two groups. Moreover, ulcer‐related symptoms, bleeding rates, adverse effects, and drug compliance were compared. Results: A total of 64 patients were enrolled. Of these, 17 patients were excluded from the study. The two groups were comparable in terms of baseline clinicopathologic characteristics. Four weeks after EMR, the two groups did not differ with respect to ulcer stage (p = .475) or ulcer‐related symptoms (p = .399). However, the ulcer reduction ratio was significantly higher in the Hp group (0.028 ± 0.024 vs. 0.065 ± 0.055, p < .05). No differences were observed between the two groups with regard to drug compliance, adverse drug event rates, or bleeding rates. Conclusions: Our results suggest that H. pylori eradication therapy might improve the ulcer healing rate after EMR.     

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia

Background

Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance.

Methods

Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby–Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed.

Results

We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement.

Conclusion

H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.     

Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection

Background

Since the ‘Fourth Chinese National Consensus Report on the management of H. pylori infection’ was published in 2012, three important consensuses (Kyoto global consensus report on H. pylori gastritis, The Toronto Consensus for the Treatment of H. pylori Infection in Adults and Management of H. pylori infection—the Maastricht V/Florence Consensus Report) have been published regarding the management of H. pylori infection.

Materials and Methods

A Delphi method was adopted to develop the consensus of relevant ‘statements’. First, the established ‘statements’ were sent to experts via email. Second, after undergoing two rounds of consultation, the initial statements were discussed face to face and revised in the conference item by item on 16 December 2016. Finally, 21 core members of conferees participated in the final vote of statements. Voting for each statement was performed using an electronic system with levels of agreements shown on the screen in real time.

Results

Consensus contents contained a total of 48 “statements” and related 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota.

Conclusions

Recommendations are provided on the basis of the best available evidence.     

Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications

Background

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori‐induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication.

Materials and Methods

Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low‐grade intraepithelial neoplasia, high‐grade intraepithelial neoplasia, and intestinal‐type gastric cancer groups. Helicobacter pylori infection was determined by either ¹³C‐urea breath test or immunohistochemistry staining.

Results

In Helicobacter pylori‐negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low‐grade intraepithelial neoplasia, and declined in high‐grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori‐infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori‐negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori‐negative control. Labeling index of Ki67 in Helicobacter pylori‐negative groups was higher in gastric cancer than chronic atrophic gastritis and low‐grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori‐positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress.

Conclusions

These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori‐induced gastric cancer.