Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

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.

Triple therapy for Helicobacter pylori eradication and the risk of hypoglycemia in patients with diabetes: a population-based cohort study.

The incidence of type 2 diabetes mellitus has risen globally, from 108 million cases in 1980 to 422 million cases in 2014. Although controlling glycemic levels in patients with diabetes is crucial, insulin and sulfonylureas can cause hypoglycemic episodes and even potentially fatal events such as comas, seizures, life-threatening arrhythmias, and myocardial infarctions. Several antibiotics have been documented to cause hypoglycemic episodes; the use of antibiotics along with insulin or sulfonylureas might further increase the risk of hypoglycemia. Therefore, researchers must determine which antibiotics carry a risk of inducing severe hypoglycemic events. The prevalence of H. pylori infection remains high in most countries, and the infection is often treated with triple therapy involving amoxicillin, clarithromycin, and a proton pump inhibitor (PPI). Several case reports have reported that hypoglycemia can occur when used with patients who also take diabetes medication. Therefore, we hypothesized that patients with diabetes have an increased risk of hypoglycemic episodes when being treated with triple therapy for H. pylori infection. By analyzing medical records from Taiwan's National Health Insurance Research Database, we found a significant association between hypoglycemia and triple therapy treatment for diabetic patients with peptic ulcer disease. Prescribing triple therapy to patients with diabetes and peptic ulcers significantly increased the risk of a hypoglycemic episode (adjusted odds ratio [aOR] = 1.75, 95% confidence interval [CI]: 1.64 to 1.88, P < 0.001). Similarly, the highest aOR (5.77, 95% CI 4.82 to 6.92) was found in patients with diabetes and peptic ulcers who had hypoglycemic episodes within 30 days after triple therapy treatment. Many patients with diabetes require H.pylori eradication for peptic ulcer treatment, and vigilance toward the risk of hypoglycemia in this population is thus necessary.

The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults.

BACKGROUND: The impact of probiotics on non-Helicobacter pylori gastric microbiota and its role in microbial restoration after eradication were relatively unknown. We aimed to explore the effect of H. pylori eradication and probiotic intervention on gastric microbiota in young adults. METHODS: Fifty-six H. pylori-negative and 95 H. pylori-positive subjects aged 19-30 were included in this study. H. pylori-infected individuals were randomly assigned to quadruple therapy, probiotics supplemented quadruple therapy, or probiotics monotherapy group. Gastric mucosa and gastric juice samples were collected before and 2 months after treatment for 16SrRNA gene sequencing. RESULTS: The gastric microbial community structure and composition differed from H. pylori-negative subjects 2 months after successful H. pylori eradication. The α diversity of gastric mucosal microbiota significantly increased and was higher than H. pylori-negative subjects, while the α diversity of gastric juice microbiota decreased and was lower than the H. pylori-negative. After probiotics supplemented eradication treatment, Bifidobacterium was enriched in gastric mucosa, Lactobacillus was enriched in gastric juice, potentially pathogenic bacteria such as Fusobacterium and Campylobacter decreased, and the microbial diversity was closer to that of H. pylori-negative subjects compared to quadruple therapy group. Probiotics monotherapy significantly altered the diversity, community structure, and composition of gastric microbiota but showed no advantage in H. pylori inhibition and upregulating beneficial bacteria such as Bifidobacterium and Lactobacillus and related metabolism pathways. Certain potentially pathogenic bacteria such as Fusobacterium increased after probiotic monotherapy. CONCLUSION: H. pylori eradication significantly disrupted gastric microbiota in young adults and could not be restored in a short time. Probiotics supplementation partially helped restore the gastric dysbiosis caused by eradication therapy, but it might be unnecessary for H. pylori-infected young adults to take probiotics alone.

Dietary multivalent anti-Helicobacter pylori immunoglobulin Y significantly increase the H. pylori eradication and improve the clinical symptoms in patients.

BACKGROUND: The oral chicken immunoglobulin Y (IgY) as a novel model of immunotherapy to control Helicobacter pylori (H. pylori, Hp) infection has gained much interest in recent years. However, none of the current IgY therapies showed a total eradication of H. pylori on patients. METHODS: In this report, the recombinant antigens of H. pylori, including UreB (1710 bp), BabA2 (1269 bp), and FlaA (399 bp), were, respectively, expressed and purified, and then mixed and subjected to immunize laying hens for the preparation of multivalent anti-H. pylori immunoglobulin Y (anti-Hp mIgY). Next, the biological activities of anti-Hp mIgY, including the recognition to antigens and the inhibition on H. pylori growth, were tested. Moreover, to perform a clinical trial, 94 Hp-infected patients, according to the values of 13 C urea breath test and the characteristics of gastroscopy of volunteers, were enrolled to evaluate the effects of dietary anti-Hp mIgY against H. pylori infection. After continuous dietary of anti-Hp mIgY for 2 weeks, the oral administration was terminated. The clinical symptoms of the patients were followed up at 2nd, 4th, and 6th week, respectively, and the 13 C urea breath test were re-examined at 6th week. RESULTS: The anti-Hp mIgY could bind to recombinant antigens very well, and the titers of anti-Hp mIgY to UreB, Baba2, and FlaA, are 62.5, 125, and 250 µg/ml, respectively. The in vitro antibacterial test showed that the 2 mg/ml of anti-Hp mIgY could completely inhibit the H. pylori growth for 36 h. After a 2-week dietary of anti-Hp mIgY, the value of 13 C urea breath test was significantly decreased by 56.0% (25.9 ± 14.1 vs 11.4 ± 9.78, p < 0.001), the total improvement rate of clinical symptoms in volunteers was 87.3%, and the H. pylori eradication rate was 30.6%. CONCLUSION: Two-week dietary of anti-Hp mIgY greatly improved the clinical symptoms and the quality of life of Hp-infected patients, and the H. pylori eradication rate reached up to 30.6%.

Searching for an optimal therapy for H pylori eradication: High-dose proton-pump inhibitor dual therapy with amoxicillin vs. standard triple therapy for 14 days.

BACKGROUND & AIMS: We compared a high-dose dual therapy (HDDT) with rabeprazole and amoxicillin and compared it with a standard triple therapy (STT) with rabeprazole, amoxicillin, and clarithromycin for 2 weeks for H pylori eradication in treatment naïve patients. METHODS: H pylori-positive patients were randomly assigned to either a rabeparzole (Pariet) 20 mg b.i.d., amoxicillin (Ospamox) 1 g b.i.d. and clarithromycin (Klacid) 500 mg b.i.d. for 14 days or rabeprazole (Pariet) 20 mg q.i.d., amoxicillin (Ospamox) 1 g q.i.d. also for 14 days. Eradication was tested for by the C13 -UBT at least 4 weeks after the completion of therapy. RESULTS: H pylori was eradicated in 86.2% of patients (81/94) (95% CI: 77.8-91.7) in the STT group compared with 92.8% (90/97) (95% CI: 85.9-96.5) in the HDDT group on ITT analysis. On PP analysis, H pylori was eradicated in 91.0% of patients (81/89) (95% CI: 83.3-95.4) in the STT group compared with 93.8% (90/96) (95% CI: 87.0-97.1) in the HDDT group. Side effects were few although many patients in the STT arm complained of bitter taste. The HDDT arm was well tolerated by patients. CONCLUSIONS: The HDDT gave a high eradication rate comparable to the STT for 2 weeks and was a well-tolerated regimen for H pylori eradication.

Effect of Helicobacter pylori infection and its eradication on gastric regenerating atypia in 22 133 subjects.

BACKGROUND AND AIM: The aim of this study was to identify factors affecting persistent gastric regenerating atypia and determine the effect of Helicobacter pylori eradication on the course of this lesion. METHODS: In cross-sectional setting, comprehensive health check-up subjects who underwent both endoscopy and H. pylori test from 2001 to 2009 were included. The association between H. pylori and gastric regenerating atypia was evaluated. In cohort setting, patients with regenerating atypia who underwent H. pylori test from 2001 to 2013 were included. Factors affecting positive pathology (persistent regenerating atypia or new development of neoplasm) in patients with regenerating atypia at baseline were investigated. RESULTS: In cross-sectional setting, regenerating atypia was observed in 1.1% (241/22 133). H. pylori infection was associated with gastric regenerating atypia (adjusted odds ratio, 1.47; 95% confidence interval [CI], 1.12-1.91). In cohort setting, 310 patients with regenerating atypia were finally eligible. Positive pathology rate during follow up was 16.1% (15/93) in the persistent infection group, 2.8% (3/106) in successful eradication group, and 4.5% (5/111) in baseline H. pylori-negative group. Persistent H. pylori infection increased the risk of positive pathology (adjusted risk ratio [RR], 7.18; 95% CI, 1.95-26.48) compared to H. pylori eradication group. Persistent H. pylori infection increased the risk of regenerative atypia (adjusted RR, 5.70; 95% CI, 1.46-22.17) and new neoplasm (adjusted RR, 10.74; 95% CI, 1.10-105.17) compared to baseline negative H. pylori. CONCLUSIONS: H. pylori infection is an independent risk factor for gastric regenerating atypia. Eradication of H. pylori seems helpful for regression of regenerating atypia.

Saccharomyces boulardii CNCM I-745 plus sequential therapy for Helicobacter pylori infections: a randomized, open-label trial.

AIM: To determine the effect of Saccharomyces boulardii CNCM I-745 (S. boulardii) plus sequential therapy on Helicobacter pylori (H. pylori) eradication rate. METHODS: This open-label prospective study randomized (1:1) patients with confirmed H. pylori infection to standard sequential therapy of twice-daily (bid) omeprazole 20 mg plus amoxicillin 1 g for 5 days, followed by bid omeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 5 days (control group), or sequential therapy plus bid S. boulardii 250 mg (experimental group). Adverse events (AEs) were recorded throughout the study, and the H. pylori eradication rate was determined 4 weeks after treatment. RESULTS: The study was conducted from May 2013 to May 2016 and included 199 patients (51.3% male; mean age 44.6 ± 13.6 years). The H. pylori eradication rate was higher in the experimental group than the control group (86.0% vs. 74.7%; P = 0.02). Compared with the control group, patients in the experimental group experienced a significantly lower overall incidence of AEs (17.0% vs. 55.7%; p < 0.001) and the incidence of antibiotic-associated diarrhea (2.0% vs. 46.4%; P = 0.02). The experimental group showed improved treatment compliance over the 10-day study period compared with the control group (95.0% vs. 91.2%, P < 0.001). CONCLUSION: Addition of S. boulardii to sequential therapy improved H. pylori eradication rate and reduced the incidence of treatment-associated AEs in Moroccan patients with H. pylori infection.

The Reduction in Gastric Atrophy after Helicobacter pylori Eradication Is Reduced by Treatment with Inhibitors of Gastric Acid Secretion.

BACKGROUND: Helicobacter pylori (H. pylori) eradication therapy may improve gastric atrophy and intestinal metaplasia, but the results of previous studies have not always been consistent. The aim of this study was to compare the histological changes of intestinal metaplasia and gastric atrophy among the use of acid-suppressing drugs after H. pylori eradication. METHODS: A cohort of 242 patients who underwent successful eradication therapy for H. pylori gastritis and surveillance endoscopy examination from 1996 to 2015 was analyzed. Changes in the histological scores of intestinal metaplasia and atrophy according to drug use (proton-pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), and non-acid suppressant use) were evaluated in biopsies of the antrum and corpus using a generalized linear mixed model in all patients. RESULTS: The mean follow-up period and number of biopsies were 5.48 ± 4.69 years and 2.62 ± 1.67 times, respectively. Improvement in the atrophy scores of both the antrum (p = 0.042) and corpus (p = 0.020) were significantly superior in patients with non-acid suppressant drug use compared with those of PPI and H2RA use. Metaplasia scores in both the antrum and corpus did not improve in all groups, and no significant differences were observed among groups in the antrum (p = 0.271) and corpus (p = 0.077). CONCLUSIONS: Prolonged acid suppression by PPIs or H2RAs may limit the recovery of gastric atrophy following H. pylori eradication.

Early detection of gastric cancer after Helicobacter pylori eradication due to endoscopic surveillance.

BACKGROUND: Helicobacter pylori eradication therapy is commonly performed to reduce the incidence of gastric cancer. However, gastric cancer is occasionally discovered even after successful eradication therapy. Therefore, we examined the prognosis of gastric cancer patients, diagnosed after successful H. pylori eradication therapy. MATERIALS AND METHODS: All-cause death rates and gastric cancer-specific death rates in gastric cancer patients who received successful H. pylori eradication treatment was tracked and compared to rates in patients who did not receive successful eradication therapy. RESULTS: In total, 160 gastric cancer patients were followed-up for up to 11.7 years (mean 3.5 years). Among them, 53 gastric cancer patients received successful H. pylori eradication therapy prior to gastric cancer diagnosis. During the follow-up period, 11 all-cause deaths occurred. In the successful eradication group, the proportion of patients with cancer stage I was higher. The proportions of patients who received curative endoscopic therapy and endoscopic examination in the 2 years prior to gastric cancer diagnosis were also higher in the successful eradication group. Kaplan-Meier analysis of all-cause death and gastric cancer-specific death revealed a lower death rate in patients in the successful eradication group (P = .0139, and P = .0396, respectively, log-rank test). The multivariate analysis showed that endoscopy within 2 years before cancer diagnosis is associated with stage I cancer. CONCLUSIONS: Possible early discovery of gastric cancer after H. pylori eradication due to regular endoscopic surveillance may contribute to better prognosis of patients with gastric cancer.

Efficacy of Helicobacter pylori eradication regimens in Rwanda: a randomized controlled trial.

BACKGROUND: Successful H. pylori treatment requires the knowledge of local antimicrobial resistance. Data on the efficacy of H. pylori eradication regimens available in sub-Saharan Africa are scant, hence the optimal treatment is unknown. Our goals were to determine the efficacy of available regimens in Rwanda as well as evaluate the effect of treatment on health-related quality of life (HRQoL) in patients undergoing esophagogastroduodenoscopy. METHODS: This is a randomized controlled trial conducted from November 2015 to October 2016 at a tertiary hospital in Rwanda. Enrollees were 299 patients (35% male, age 42 ± 16 years (mean ± SD)) who had a positive modified rapid urease test on endoscopic biopsies. After a fecal antigen test (FAT) and HRQoL assessment by the Short Form Nepean Dyspepsia Index (SF-NDI) questionnaire, patients were randomized 1:1:1:1 to either a triple therapy combining omeprazole, amoxicillin and one of clarithromycin/ciprofloxacin/metronidazole or a quadruple therapy combining omeprazole, amoxicillin, ciprofloxacin and doxycycline. All therapies were given for a duration of 10 days. The outcome measures were the persistence of positive FAT (treatment failure) 4 to 6 weeks after treatment and change in HRQoL scores. RESULTS: The treatment success rate was 80% in the total population and 78% in patients with a history of prior triple therapy. Significant improvement in HRQoL in the total group (HRQoL mean scores before and after treatment respectively: 76 ± 11 and 32 ± 11, p < 0.001) and the group with functional dyspepsia (HRQoL mean scores before and after treatment respectively: 73 ± 11 and 30 ± 9, P < 0.001) was observed across all treatment groups. Using clarithromycin based triple therapy (standard of care) as a reference, the group treated with metronidazole had worse HRQoL (p = 0.012) and had a trend towards worse treatment outcome (p = 0.086) compared to the ciprofloxacin based combination therapies. CONCLUSION: Clarithromycin and ciprofloxacin based combination therapies are effective and safe to use alternatively for H. pylori eradication and improve HRQoL. Among the regimens studied, metronidazole based triple therapy is likely to be clinically inferior. TRIAL REGISTRATION: The clinical trial was retrospectively registered ( PACTR201804003257400 ) with the Pan African Clinical Trial Registry database, on April 6th, 2018 in South Africa.

Helicobacter pylori Eradication Therapy Ameliorates Latent Digestive Symptoms in Chronic Atrophic Gastritis.

BACKGROUND/AIMS: This study investigated the effect of Helicobacter pylori eradication therapy on latent digestive symptoms in chronic atrophic gastritis. METHODS: We enrolled 650 health checkup patients who underwent eradication therapy for chronic gastritis and completed a self-report questionnaire before and after the treatment between January 2014 and December 2016 at the Japanese Red Cross Society Kyoto Daiichi Hospital. RESULTS: H. pylori eradication therapy for chronic atrophic gastritis improved latent digestive symptoms, including both the acid reflux and dyspepsia components in the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) scores. The effect was sustained until 1 year after the treatment. Higher FSSG scores (≥8 points) before H. pylori eradication therapy and age <70 years were significantly associated with the improvement of digestive symptoms after H. pylori eradication therapy. CONCLUSION: H. pylori eradication therapy may improve patients' quality of life through the resolution of latent abdominal symptoms.

Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases.

Although proton pump inhibitors (PPIs) have been used widely, acid-related diseases are still associated with a huge burden on the health care system. Recently, the efficacy and safety of a new acid suppressant named vonoprazan in the treatment of acid-related diseases have been evaluated by a series of studies. As a novel potassium-competitive acid blocker, vonoprazan may provide reversible acid suppression by preventing K+ from binding to gastric H+/K+-ATPase. It has been clinically used for the short-term treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Helicobacter pylori (H. pylori) infection in Japan. The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively; also, it is effective in curing PPI-resistant GERD. It increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy. It is also effective in the eradication of clarithromycin-resistant H. pylori strains. All of these short-term studies show vonoprazan is safe and well-tolerated. As a safe and effective acid inhibitor, vonoprazan might be a novel alternative in the treatment of acid-related diseases.

High primary antibiotic resistance of Helicobacter Pylori strains isolated from dyspeptic patients: A prevalence cross-sectional study in Spain.

BACKGROUND: The rate of H. pylori resistance to different antibiotics is increasing and determines the selection of eradication therapy. The aim of this study was to determine the resistance patterns of H. pylori strains in our area. METHODS: Biopsies from gastric corpus for microbiological culture and antibiotic resistance were obtained in patients undergoing upper gastrointestinal endoscopy for dyspepsia. Selective Agar Pylori for isolation of the bacteria and Agar Mueller-Hinton supplemented with blood to test the sensitivity to antibiotics were used. Presence of H. pylori was confirmed using direct observation with phase-contrast microscopy and/or smears stained with acridine orange. In vitro bacterial susceptibility to amoxicillin, clarithromycin, rifampicin, tetracycline, metronidazole, and levofloxacin was tested using diffusion MIC test strips. Minimum inhibitory concentration values were determined based on the 6th version of the EUCAST (European Committee on Antimicrobial Susceptibility Testing) Clinical Breakpoint (2016). RESULTS: Two hundred and seventeen patients were included (58.1% female, median age 64 years, range 25-92). H. pylori was identified in 108 patients (49.8%); culture and antibiogram were completed in 77 of them (71.3% of H. pylori-positive patients). The resistance rates were as follows: levofloxacin 38.7%, rifampicin 33.3%, metronidazole 27% and clarithromycin 22.4%. No case of amoxicillin or tetracycline resistance was identified. Dual clarithromycin-metronidazole resistance was observed in 10% of strains, whereas multiple drug-resistant was observed in 14.2%. CONCLUSIONS: Resistance rate of H. pylori to antibiotics is high in the northwest of Spain. The high resistance to levofloxacin and clarithromycin advises against their wide empirical use of these antibiotics in eradication regimens.

Helicobacter pylori infection is associated with reduced prevalence of colonic diverticular disease.

BACKGROUND: Colonic diverticular disease is a common disorder with increasing incidence in Western societies. The intestinal microbiome may be among etiological factors. Helicobacter pylori may protect against some intestinal diseases, and incidence of H. pylori is decreasing in Western societies. Thus, we aimed to determine whether H. pylori is associated to decreased prevalence of registered colonic diverticular disease. MATERIALS AND METHODS: In a historical cohort study, patients were enrolled from primary health care centers after urea breath test for H. pylori and then followed for a median of 6 years. The patient's diagnostic codes and country of birth were acquired from nationwide Danish administrative registries. We used logistic regression to compare prevalence and Cox regression to compare incidence of diverticular disease between H. pylori-positive and H. pylori-negative patients, adjusting for confounding variables. RESULTS: Patients infected with H. pylori had lower prevalence of colonic diverticular disease (0.87% vs 1.14%, OR=0.62, 95% CI: 0.50-0.78). This phenomenon was observed whether we studied all registered diagnoses or only cases registered as primary diagnoses at discharge. After urea breath test, we observed no statistical difference in incidence rates of diverticular disease. CONCLUSION: H. pylori is associated with reduced prevalence of colonic diverticular disease. The inverse association was absent after the urea breath test. Thus, we speculate that H. pylori may provide protection from colonic diverticular disease. Alternatively, H. pylori is a marker for other factors affecting disease development.

Magnifying NBI Patterns of Gastric Mucosa After Helicobacter pylori Eradication and Its Potential Link to the Gastric Cancer Risk.

BACKGROUND: Gastric cancer develops after successful H. pylori eradication in patients with severe atrophic gastritis. We classified atrophic and non-atrophic mucosa of gastric body using magnifying NBI endoscopy in patients after successful H. pylori eradication. MATERIALS AND METHODS: One hundred and twenty-five patients after successful H. pylori eradication (median period after eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved gastric body were divided into the following: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. The subjects were also classified into the three types: Grade 0-restored pattern is shown in all or almost the entire area of gastric body; Grade 1-mixture of restored and atrophic pattern, there is a considerable portion of the atrophic area in the lesser curvature; Grade 2-atrophic pattern is shown in all or almost the entire area of the gastric body. RESULTS: Sensitivity and specificity for atrophic type for detection of histological intestinal metaplasia were 95.9 and 98.3%, respectively. No association was observed between the prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1 and 2 were significantly frequent in gastric cancer patients diagnosed both before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer-free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in patients who underwent H. pylori eradication for gastric ulcer. CONCLUSIONS: Magnifying the NBI pattern well correlates with pathological status of gastric mucosa after H. pylori eradication and may predict gastric cancer occurrence.

Gastric Juice-Based Real-Time PCR for Tailored Helicobacter Pylori Treatment: A Practical Approach.

A gastric juice-based real-time polymerase chain reaction (PCR) assay was established to identify Helicobacter pylori infection, clarithromycin susceptibility and human CYP2C19 genotypes and to guide the choice of proton pump inhibitor (PPI), clarithromycin and amoxicillin treatment for tailored H. pylori eradication therapy. From January 2013 to November 2014, 178 consecutive dyspeptic patients were enrolled for collection of gastric biopsy samples and gastric juice by endoscopy at the Peking University Third Hospital; 105 and 73 H. pylori-positive and -negative patients, respectively, were included in this study. H. pylori infection was defined as samples with both a strongly positive rapid urease test (RUT) and positive H. pylori histology. A series of primers and probes were distributed into four reactions for identifying the H. pylori cagH gene coupled with an internal control (Rnase P gene), A2142G and A2143G mutants of the H. pylori 23S rRNA gene, and single-nucleotide polymorphisms (SNPs) G681A of CYP2C19*2 and G636A of CYP2C19*3. The E-test and DNA sequencing were used to evaluate the H. pylori clarithromycin susceptibility phenotype and genotype. The SNPs CYP2C19*2 and CYP2C19*3 were also evaluated by nucleotide sequencing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this gastric juice-based real-time PCR assay were evaluated by comparing with the same measures obtained through gastric biopsy-based PCR and culture. The H. pylori diagnostic sensitivities of the culture, PCR, and gastric biopsy- and gastric juice-based real-time PCR assays were 90.48% (95/105), 92.38% (97/105), 97.14% (102/105) and 100% (105/105), respectively; the specificities of the above methods were all 100%. Higher false-negative rates were found among the gastric biopsy samples assessed by culture (10.48%, 11/105), PCR (7.62%, 8/105) and real-time PCR (2.86%, 3/105) than in gastric juice by real-time PCR. Regarding clarithromycin susceptibility, a concordance of 82.98% (78/94) and discordance of 17.02% (16/94) were observed among the different methods, discrepancies that mainly represent differences between the H. pylori clarithromycin susceptibility phenotype and genotype. Three coinfections of susceptible and resistant strains were detected, with resistant-to-susceptible ratios of 1.16, 3.44, and 8.26. The CYP2C19 genotyping results from gastric juice by real-time PCR were completely in accordance with those obtained from biopsy samples by conventional PCR. This gastric juice-based real-time PCR assay is a more accurate method for detecting H. pylori infection, clarithromycin susceptibility and CYP2C19 polymorphisms. The method may be employed to inform the choice of proton pump inhibitor (PPI), clarithromycin and amoxicillin treatment for tailored H. pylori eradication therapy.

Management of adult primary immune thrombocytopenia based on Japanese clinical guides.

Primary immune thrombocytopenia (also known as idiopathic thrombocytopenic purpura; ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. The therapeutic goal of ITP is not to normalize the platelet count, but to elevate the platelet count to a safe range (above 30×103/µl) to minimize the risk of bleeding and to minimize the side effects of drugs such as corticosteroids and TPO receptor agonists (TPORAs). In 2011, TPORAs were approved for the management of refractory ITP in Japan. To announce the proper use of TPORAs, we have published a practical guide for the management of adult primary ITP and primary ITP during pregnancy in 2012 and 2014, respectively, as a study group of the Specific Disease Treatment Research Program for Intractable Diseases of the Ministry. Notably, Helicobacter pylori eradication was approved for the management of ITP in 2010 in Japan. Because there was no evidence based on the prospective randomized controlled trials regarding the management of ITP during pregnancy, we conducted several meetings to obtain a consensus among hematologists, obstetricians, pediatricians, and anesthesiologists. In this paper, I have reviewed the practical guides for the management of adult ITP.

Proton pump inhibitors and risk of periampullary cancers--A nested case-control study.

Considerable attention has been focused on long-term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA-damaged cells. The aim of this study is to examine the dose-dependent effect of PPI on periampullary cancers in a national population-based cohort. A nested case-control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A "PPI user" was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow-up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16-1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose-dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long-term PPI use was associated with an increased risk of periampullary cancers in the current population-based study. Physicians must weigh potential risks of long-term maintenance against therapeutic benefit.

Challenges to the Treatment and New Perspectives for the Eradication of Helicobacter pylori.

Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.