The nonadherence and risk factors of eradication failure by sequential therapy as first-line anti-Helicobacter pylori treatment in real-world clinical practice.

BACKGROUND: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. MATERIALS AND METHODS: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. RESULTS: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). CONCLUSIONS: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.

Investigation into the content of red material in EUS-guided pancreatic cancer biopsies.

BACKGROUND AND AIMS: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. METHODS: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. RESULTS: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm2 and 10.74 mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] µg vs .70 [interquartile range, .27-1.24] µg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001). CONCLUSIONS: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Transferrin and Prealbumin Identify Esophageal Cancer Patients with Malnutrition and Poor Prognosis in Patients with Normal Albuminemia: A Cohort Study.

In this study, we aimed to analyze whether serum prealbumin and transferrin have a higher sensitivity than albumin for detecting malnutrition and predicting survival in esophageal cancer patients. A total of 212 patients were prospectively enrolled. Serum albumin, prealbumin, and transferrin were analyzed by enzyme-linked immunosorbent assays. The association of nutritional markers with survival was analyzed. We found that malnutrition was presented in 44.5% of the patients, while 56.6% were unaware of their body weight change. The area under the curve for diagnosing malnutrition was largest for prealbumin, followed by transferrin and albumin, with optimal breakpoints of 21 mg/dL, 206 mg/dL, and 4.3 g/dL, respectively, for diagnosing malnutrition. The diagnostic sensitivity for malnutrition was 34.1-63.4% with a single marker and this increased to 80.5% with all 3 markers. In patients with normal albuminemia (≥ 4.3 g/dL), a low level of prealbumin and/or transferrin predicted malnutrition and poor prognosis. Multivariate Cox regression analysis confirmed that a low level of the nutritional marker was an independent poor prognostic factor. In conclusion, serum prealbumin and transferrin outperformed albumin in identifying esophageal cancer patients with malnutrition and poor prognosis. Checking all three markers will help with the early diagnosis of malnutrition and enable timely intervention.

Atrophic gastritis in Helicobacter pylori-infected children.

BACKGROUND: Helicobacter pylori infection is the leading cause of peptic ulcer and chronic gastritis and may initiate gastric carcinogenesis following the Correa cascade. Another lineage of metaplasia, spasmolytic peptide-expressing metaplasia (SPEM) has recently been found to be an alternative precursor to gastric cancer. To date, few reports have investigated gastric precancerous lesions among children with H. pylori infection. This study aimed to evaluate the histopathological pattern of H. pylori atrophic gastritis in children and the extent of precancerous lesions. MATERIALS AND METHODS: This study enrolled pediatric patients with H. pylori infection from 1998 to 2019. During esophagogastroduodenoscopy examinations, biopsy fragments were collected from the gastric antrum and corpus for rapid urease test, culture, and histology evaluation. The presence and degree of chronic inflammation, activity of gastritis, H. pylori density, atrophy, and intestinal metaplasia (IM) were assessed according to the modified Updated Sydney System. Trefoil factor 2 (TFF2) immunohistochemistry was also performed to assess SPEM in the gastric tissues collected from each case using rabbit anti-human TFF2 antibodies. RESULTS: A total of 92 children with H. pylori infection and adequate gastric mucosa biopsies were enrolled. Esophagogastroduodenoscopy showed that 39 (42.4%) had duodenal ulcers, 11 (12.0%) had gastric ulcers, 41 (44.6%) had gastritis, and 1 (1.1%) had negative findings. Mild-to-moderate IM was identified in 4 patients (4.3%). SPEM was found in 8 patients (8.7%) with a significantly higher incidence among female patients (15.8% vs. 8.7%, p = .031). Gastric glandular atrophy presented in 28 patients (30.4%), and high-grade atrophy was more common in female patients (3.2% vs. 1.9%, p = .031). CONCLUSIONS: The prevalence rates of atrophic gastritis in the children with H. pylori infection were 30.4% for gastric glandular atrophy, 4.3% for IM and 8.7% for SPEM. SPEM and high-grade atrophy were more common in female patients.

Endoscopic ultrasound avoids adverse events in high probability choledocholithiasis patients with a negative computed tomography.

BACKGROUND: The current guideline recommends patients who meet high probability criteria for choledocholithiasis to receive endoscopic retrograde cholangiopancreatography (ERCP). However, adverse events can occur during ERCP. Our goal is to determine whether endoscopic ultrasound (EUS) before ERCP can avoid unnecessary ERCP complications, especially in patients with a negative CT scan. METHODS: A total of 604 patients with high probability of choledocholithiasis were screened and 104 patients were prospectively enrolled. Patients with malignant biliary obstruction, altered GI anatomy, and choledocholithiasis on CT scan were excluded. Among them, 44 patients received EUS first, and ERCP if choledocholithiasis present (EUS-first group). The other 60 patients received ERCP directly (ERCP-first group). The baseline characteristics, presence of choledocholithiasis, and complications were compared between groups. All patients were followed for 3 months to determine the difference in recurrent biliary event rate. Cost-effectiveness was compared between the two strategies. RESULTS: There was no marked difference in age, sex, laboratory data, presenting with pancreatitis, and risk factors for choledocholithiasis. Overall, 51 patients (49.0%) had choledocholithiasis, which did not justify the risk of direct ERCP. In the EUS-first group, 27 (61.4%) ERCP procedures were prevented. The overall complication rate was significantly lower in the EUS-first group compared to the ERCP-fist group (6.8% vs. 21.7%, P = 0.04). The number-needed-to-treat to avoid one unnecessary adverse event was 6.71. After a 3-month follow-up, the cumulative recurrence biliary event rates were similar (13.6% vs. 15.0%, P = 0.803). EUS-first strategy was more cost-effective than the ERCP-first strategy (mean cost 2322.89$ vs. 3175.63$, P = 0.002). CONCLUSIONS: In high-probability choledocholithiasis patients with a negative CT, the EUS-first strategy is cost-effective, which can prevent unnecessary ERCP procedures and their complications.

An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding.

BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients.

BACKGROUND: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. METHODS: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. RESULTS: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. CONCLUSION: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy.

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B12 is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B12 supplementation and intramuscular administration of vitamin B12 are equally effective in the treatment of vitamin B12 deficiency.

Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen.

PURPOSE: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. METHODS: We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. RESULTS: The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025). CONCLUSION: Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

H. pylori isolates with amino acid sequence polymorphisms as presence of both HtrA-L171 & CagL-Y58/E59 increase the risk of gastric cancer.

BACKGROUND: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. METHODS: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. RESULTS: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1-6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001). CONCLUSIONS: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.

Increasing antimicrobial resistance to clarithromycin and metronidazole in pediatric Helicobacter pylori infection in southern Taiwan: A comparison between two decades.

BACKGROUND: Antimicrobial resistance of Helicobacter pylori reduces the eradication rate. This study aimed to investigate changes in antimicrobial susceptibility of H pylori isolated from children in Taiwan in the past two decades. METHODS: This study enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a national tertiary referring hospital from 1998 to 2018. H pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E test. The antibiotic resistance rates and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018. RESULTS: A total of 70 Helicobacter pylori isolates (29 from 1998 to 2008 and 41 from 2009 to 2018) were identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n = 31), gastric ulcers (n = 9), and gastritis (n = 30). The overall antimicrobial resistance rates of clarithromycin and metronidazole were 22.9% and 21.4%, respectively. The dual resistance rate of clarithromycin and metronidazole was 10%. Resistance rates of levofloxacin and amoxicillin were 8.3% and 2.9%, respectively. None of the isolates were resistant to tetracycline. Compared with the isolates from 1998 to 2008, those from 2009 to 2018 had higher MICs and resistance rates of clarithromycin (26.8% vs 17.2%, P = 0.35) and metronidazole (26.8% vs 13.8%, P = 0.19), but not levofloxacin (9.8% vs 5.3%, P = 1.0) or coresistance to clarithromycin and metronidazole (12.2% vs 6.9%, P = 0.69). CONCLUSIONS: The antimicrobial resistance rates of pediatric H pylori isolates to clarithromycin and metronidazole increased during the past decade. The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H pylori eradication rates.

Spasmolytic polypeptide-expressing metaplasia associated with higher expressions of miR-21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives.

BACKGROUND AND AIMS: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication. METHODS: We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication. RESULTS: GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P < 0.01) than controls. The tissue miR-21, 155, and 223 in antrum were higher in cases with SPEM than in those without SPEM (P <= 0.05). There was similar SPEM reversibility after H pylori eradication between GCF subjects and controls (72% vs 69%, P = 0.852). In the SPEM regressed cases, tissue miR-21, 155, and 223 decreased after H pylori eradication (P < 0.05). CONCLUSION: The H pylori-infected GCF subjects were prone to have SPEM with higher tissues miR-21, 155, and 223 expressions. H pylori eradication can result in a 70% SPEM regression, accompanied by a decline in miR-21, 155, and 233 expression levels.

Lead Time Bias May Contribute to the Shorter Life Expectancy in Post-colonoscopy Colorectal Cancer.

BACKGROUND: The long-term outcomes of post-colonoscopy colorectal cancer have varied in previous studies. Our nationwide cohort analysis estimated expected years of life lost to adjust for lead time bias. AIM: We recalculated the long-term outcomes for post-colonoscopy and detected colorectal cancer. METHODS: Patients with colorectal cancer registered in the Taiwan Cancer Registry between 2002 and 2009 were enrolled. The detected group included 22,169 cases of colorectal cancer confirmed within 6 months after a colonoscopy. The post-colonoscopy group included 1653 cancer patients who received a colonoscopy 6-60 months before diagnosis. Patients were followed up until 2011. We simulated age-, sex-, and calendar year-matched referents from life tables in the Taiwan National Vital Statistics using a Monte Carlo method. The life expectancy and expected years of life lost of the cancer patients were obtained from extrapolation of the logit transformation of the survival ratio between the cancer cohorts and the referent groups. RESULTS: Post-colonoscopy colorectal cancer had shorter life expectancies than detected cancer (stages 2-4: 13.6 vs. 16.1 years; 8.7 vs. 12.6 years; 2.1 vs. 4.1 years, p < 0.001). The loss-of-life expectancy did not show this trend after adjusting for lead time bias. Post-colonoscopy colorectal cancer was found at an older age, more often proximal, and was associated with previous endoscopic polypectomy procedures (p < 0.001). CONCLUSIONS: Post-colonoscopy colorectal cancer leads to a shorter life expectancy, which appears partially explained by the presence of lead time bias. Quality assurance for colonoscopy and close surveillance for high risk groups would reduce post-colonoscopy colorectal cancer.

Maternal H. pylori seropositivity is associated with gestational hypertension but is irrelevant to fetal growth and development in early childhood.

BACKGROUND: Helicobacter pylori infection is known to alter growth-related hormones and affect growth in young children. However, it is still unknown whether maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and whether this can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development. METHODS: In this prospective cohort study, we recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined as > 12 U/ml of anti-H. pylori IgG in maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. The growth of the included neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth. RESULTS: Of the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p = 0.04) and lower cord blood levels of IGF-1 (< 35 ng/ml, 70.0% vs. 40.7%, p = 0.02) and IGFBP-3 (< 1120 ng/ml, 100.0% vs. 76.3%, p = 0.02) compared with the seronegative women. No significant impacts on birth weight, childhood growth and cognitive development were found to be correlated with maternal H. pylori seropositivity during pregnancy. CONCLUSIONS: Maternal H. pylori infection during pregnancy was more likely to lead to the development of GH, but was not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for mothers with H. pylori infection.

The impacts of H. pylori virulence factors on the development of gastroduodenal diseases.

Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

The implementation of the consensus on the management of Helicobacter pylori and barriers to consensus.

BACKGROUND: A consensus on the management of Helicobacter pylori has been developed. We aimed to assess whether dissemination through continuing medical education (CME) could enhance the adoption of this consensus among clinicians and to explore potential barriers to acceptance. MATERIALS AND METHODS: Four CME courses were held to disseminate the consensus. Adoption surveys were performed to evaluate participants' behavior in the past and their commitment to adopt the consensus in future clinical practice after CME. The gaps and barriers to adoption were also surveyed. RESULTS: A total of 240 physicians had attended the CME courses and received surveys with the 22 statements/substatements of the consensus. Before CME, adoption was good in six, fair in ten, and poor in six. After CME, 21 statements had either an initial >90% adoption or improvement to good or fair (P < 0.001), but one still had poor even though it showed improvement (P = 0.02). Although commitment was good or fair after CME, there was a >20% gap between "commitment" and "no barrier" to adoption for 11 statements, ten of which had a main barrier of financial incentives. Among the statements with fair or poor commitment after CME, less commitment to adoption and more barriers related to financial incentives were pronounced in clinicians serving in regional/district hospitals or clinics compared to those serving in medical centers. CONCLUSIONS: Continuing medical education may improve the adoption of the H. pylori consensus. The financial incentives were shown to be a main barrier to adoption of the consensus and should be improved.