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Background: Motility mediated by the flagella of Helicobacter pylori has been shown to be required for normal colonization and is thought to be important for the bacteria to move toward the gastric mucus in niches adjacent to the epithelium. Barnard et al. showed that CsrA appears to be necessary for full motility and the ability to infect mice, but its mechanism of regulation is still unclear., Methods: Motility and cell adhesion ability were determined in wild-type, csrA mutant, and revertant J99 strains. The bacterial shape and flagellar structure were evaluated by transmission electron microscopy. The expression of two major flagellins, flaA/flaB, and the alternative sigma factor rpoN (σ(54)) were determined by real-time quantitative RT-PCR and Western blot., Results: The csrA mutant showed loss of motility and lower adhesion ability compared with the wild-type and revertant J99 strains. The csrA mutant was not flagellated. Transcription of flaA and flaB mRNA decreased to only 40% and 16%, respectively, in the csrA mutant compared with the wild-type J99 (p = .006 and <.0001, respectively), and Western blot analysis showed dramatically reduced FlaA/FlaB proteins in a csrA mutant. The disruption of csrA also decreased expression of rpoN to 48% in the csrA mutant, but the degradation rate of rpoN mRNA was not changed., Conclusion: These results suggest that CsrA regulates H. pylori J99 flagella formation and thereby affects bacterial motility., (© 2014 John Wiley & Sons Ltd.)

The transcriptional network of the SRY (sex determining region Y)-box 17 (SOX17) and the prognostic impact of SOX17 protein expression in human cancers remain largely unclear. In this study, we evaluated the prognostic effect of low SOX17 protein expression and its dysregulation of transcriptional network in esophageal squamous cell carcinoma (ESCC). Low SOX17 protein expression was found in 47.4% (73 of 154) of ESCC patients with predicted poor prognosis. Re-expression of SOX17 in ESCC cells caused reduced foci formation, cell motility, decreased ESCC xenograft growth and metastasis in animals. Knockdown of SOX17 increased foci formation in ESCC and normal esophageal cells. Notably, 489 significantly differential genes involved in cell growth and motility controls were identified by expression array upon SOX17 overexpression and 47 genes contained putative SRY element in their promoters. Using quantitative chromatin immunoprecipitation-PCR and promoter activity assays, we confirmed that MACC1, MALAT1, NBN, NFAT5, CSNK1A1, FN1 and SERBP1 genes were suppressed by SOX17 via the SRY binding-mediated transcriptional regulation. Overexpression of FN1 and MACC1 abolished SOX17-mediated migration and invasion suppression. The inverse correlation between SOX17 and FN1 protein expression in ESCC clinical samples further strengthened our conclusion that FN1 is a transcriptional repression target gene of SOX17. This study provides compelling clinical evidence that low SOX17 protein expression is a prognostic biomarker and novel cell and animal data of SOX17-mediated suppression of ESCC metastasis. We establish the first transcriptional network and identify new suppressive downstream genes of SOX17 which can be potential therapeutic targets for ESCC., (© 2013 UICC.)

Aim: To determine whether Helicobacter pylori (H. pylori)-infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin., Methods: This longitudinal cohort study with one-year follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after one-year follow-up were compared between successful eradicated H. pylori-infected children and controls., Results: In the observation cohort, the H. pylori-infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori-infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori-infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up., Conclusion: H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.

Background: Intragenomic recombination between babA and babB mediates antigenic variations and may help H. pylori colonization. This study determined whether variable genotypes of babA and babB correlate to different clinical disease outcomes, and can distribute over the different gastric niches., Results: This study enrolled 92 clinical strains (45 from peptic ulcer, 27 from gastritis, and 20 from gastric cancer) to detect whether the babA and babB are at locus A or B by PCR reactions using the primers designed from the upstream and variable region of the babA and babB genes. Four genotypes of babA and babB (A B, AB B, A AB, AB AB) were found. The distribution of the 4 genotypes in 92 clinical strains was significantly different among patients with different gastric diseases (p < 0.05). The isolates from gastric cancer patients had a higher rate of AB AB genotype than those from non-cancer patients (40.0% vs. 9.7%, p < 0.05). The AB AB genotype was associated with a higher intensity of intestinal metaplasia (p < 0.05), but did not correlate with a higher inflammation and colonization density in gastric histology (p > 0.05). Besides, the study enrolled 19 patients to verify whether variable genotypes of babAB existed in the different gastric niches. Among the patients infected with more than one babAB genotypes over antrum and corpus, there were higher rate of genotypes as A B or AB AB in isolates from antrum than in those from corpus (75.0 % vs. 16.7%, p < 0.05)., Conclusions: The H. pylori isolate with the AB AB genotype correlates with an increased gastric cancer risk, and colonize in an antrum predominant manner.

Background: H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways., Results: Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100) of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting., Conclusions: H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Background: Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use., Aims: This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers., Methods: The 126 gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined with two factors n = 50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining., Results: Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P < 0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1 than H. pylori-infected gastric ulcers (P < 0.05)., Conclusions: H. pylori-infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID-related ulcers. In patients with the two combined factors, ulcer location and MMP-7 and MMP-9 intensities are similar to NSAID use.

Background: Osteopontin (OPN) is involved in the gastric cancer progression. The study validated whether OPN expressions correlate with Helicobacter pylori-related chronic gastric inflammation and the precancerous change as intestinal metaplasia (IM)., Methods: This study included 105 H. pylori-infected patients (63 without and 42 with IM) and 29 H. pylori-negative controls. In each subject, the gastric OPN expression intensity was evaluated by immunohistochemistry, and graded from 0 to 4 for the epithelium, lamina propria, and areas with IM, respectively. For the H. pylori-infected subjects, the gastric inflammation was assessed by the Updated Sydney System. Forty-nine patients received follow-up endoscopy to assess OPN change on gastric mucosa after H. pylori eradication. The in vitro cell-H. pylori coculture were performed to test the cell origin of OPN., Results: The H. pylori-infected patients had higher gastric OPN expression than the noninfected controls (p < .001). For the H. pylori-infected patients, an increased OPN expression correlated with more severe chronic gastric inflammation (p < .001) and the presence of IM (OR: 2.6, 95% CI: 1.15-5.94, p = .02). Within the same gastric bits, lamina propria expressed OPN stronger than epithelium (p < .001), suggesting OPN predominantly originates from inflammatory cells. The in vitro assay confirmed H. pylori stimulate OPN expression in the monocytes, but not in the gastric epithelial cells. After H. pylori eradication, the gastric OPN expression could be decreased only in areas without IM (p < .05)., Conclusions: Increased gastric OPN expression by H. pylori infection can correlate with a more severe gastric inflammation and the presence of IM., (© 2011 Blackwell Publishing Ltd.)

Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of mortality. Infusion with proton pump inhibitors (PPIs) prevents recurrent bleeding after successful endoscopic therapy. A gastric acidic environment of less than pH 5.4 alters coagulation function and activates pepsin to disaggregate platelet plugs. Gastric acid is secreted by H(+), K(+)-ATPase, naming the proton pump. This update review focuses on the mechanism and the role of PPIs in the clinical management of patients with peptic ulcer bleeding. An intravenous omeprazole bolus followed by high-dose continuous infusion for 72 h after successful endoscopic therapy can prevent the recurrent bleeding. In the Asian, however, the infusion dosage can possibly be diminished whilst preserving favorable control of the intragastric pH and thereby still decreasing rates of recurrent bleeding. Irrespective of the infusion dosage of PPIs, rates of recurrent bleeding remain high in patients with co-morbidities. Because recurrent peptic ulcer bleeding may be prolonged in those with co-morbidities, a low-dose infusion of IV PPIs for up to 7-day may result in better control of recurrent bleeding of peptic ulcers. Due to the inter-patient variability in CYP2C19 genotypes, the infusion form of new generation PPIs, such as esomeprazole, should be promising for the prevention of recurrent bleeding. This article offers a comprehensive review of clinical practice, highlighting the indication, the optimal dosage, the duration, and the potential limitation of PPIs infusion for peptic ulcer bleeding.

Background: Helicobacter pylori (H. pylori) infection up-regulates the expression of matrix metalloproteinases (MMPs), which may be involved in chronic inflammation, ulceration, and even cancer development. This study aimed to test if serum levels of MMP-3, -7, and -9 are correlated with different clinical outcomes in H. pylori-infected subjects and if these are predictive of progression to H. pylori-related gastric cancer., Method: Two hundred one patients, 28 with H. pylori-negative gastritis and 173 with different H. pylori-positive gastrointestinal diseases (46 gastritis, 43 duodenal ulcers, 29 gastric ulcers, and 55 gastric cancers) were assessed for serum MMP-3, -7, and -9 titers by enzyme-linked immunosorbent assay and validated to their correlations with the different clinical features and survival of patients with H. pylori-positive gastric cancer., Results: Among the H. pylori-infected subjects, gastric cancer patients had higher serum levels of MMP-3 and MMP-7 than those with duodenal ulcer and gastritis (P < 0.05). For gastric cancer patients, concomitant elevated MMP-3 (>14 ng/ml) and MMP-7 (>4.5 ng/ml) independently correlated with lymph node invasion (P < 0.05) and could be predictive to have shorter 2- or 5-year survivals (log rank test, P = 0.006)., Conclusion: Concomitant elevations of MMP-3 and MMP-7 serum levels in the H. pylori-infected gastric cancer patients could serve as potential biomarkers to correlate with poor survival.

After Helicobacter pylori enters the stomach, three steps are vital for infection: (i) establishing colonization; (ii) evading host immunity; and (iii) invading gastric mucosa; the last step is what is associated with diverse outcomes. Urease activity and motility mediated by the flagella of H. pylori are important in harboring colonies beneath the gastric mucus in niches adjacent to the epithelium. Several putative adhesins attach the organism to the gastric epithelium and prompt the succeeding processes for evading host immunity and invading the mucosa. Successful colonization is thus the leading and critical step. From another point of view, this can be a novel target to control this common and important infection. This review summarizes the putative adhesins that influence the evasion of host immunity, and how these could determine different clinico-pathologic outcomes. The putative adhesins include the interplay between bacterial and host Lewis antigens (type I: Le(a) and Le(b); type II: Le(x) and Le(y)), the dominant pathway between BabA and Le(b), the SabA adhesin binding to sialylated Le(x) that is upregulated in inflamed gastric tissue or those with weak-Le(b), the CagL apparatus to adapt with the alpha5beta1 integrin to mediate a type IV secretory system for CagA translocation into the epithelium; and other outer membrane proteins as HopZ, AlpA/AlpB, or OipA, without known corresponding receptors. This review implicates the adhesins vital for bugs that could be alternatively provided as novel targets for us to overcome the colonization.

Background: Peristomal infection is common after percutaneous endoscopic gastrostomy. This study aims to evaluate the correlation between airway and peristomal infected pathogens., Methods: Before the procedure, sputum cultures were prospectively performed for the patients with airway symptoms. All the patients received prophylactic antibiotics. Once peristomal infection occurred, the wound cultures were obtained to analyze the antibiotic susceptibilities of the pathogens. The paired isolates, with concordance between sputum and wound cultures, were validated for their clone identity using pulsed-field gel electrophoresis., Results: One hundred twelve patients were enrolled, and 30 patients had peristomal infection. The 31 patients with airway pathogens had a 10-fold higher risk of peristomal infection than the other 81 without airway pathogens (95% CI, 3.85-26.4, p < 0.001). Among patients collected with paired isolates from wound and sputum, 85% had concordant microorganism species. In the paired concordant isolates, 94% had indistinguishable antibiogram, and nearly 90% were clonally identical in pulsed-field gel electrophoresis., Conclusions: Patients with airway infection have an increased risk of peristomal infection after percutaneous endoscopic gastrostomy. Concerning the high concordance between infected wound and sputum isolates of such patients, the selection of appropriate prophylactic antibiotics could be individual to cover the microorganisms isolated from sputum.

Background and Aim: The intestinal metaplasia (IM) has overexpressions of cyclooxygenase-2 (COX-2) and beta-catenin. This pilot study assessed whether celecoxib, a selective COX-2 inhibitor, could regress IM that persisted long term after Helicobacter pylori eradication., Methods: Thirty-three patients with H. pylori eradication were enrolled in the present study due to the persistence of IM after a 3-year follow up. These patients received celecoxib 200 mg/day for 8 weeks, and were serially checked for levels of blood urea nitrogen and creatinine once per 2 weeks. After 8-week celecoxib treatment, IM regression was assessed by panendoscopy. The gastric specimens, taken before and after celecoxib, were immunochemically stained for COX-2 and beta-catenin., Results: The intention-to-treat and per-protocol analyses to the rates of IM regression by 8-week celecoxib treatment were 24.2% (8/33) and 28.6% (8/28), respectively. All enrolled patients had no renal impairment. Even in the patients without total IM regression, mean IM scores in the antrum decreased after 8-week celecoxib treatment (P = 0.007). The patients with complete regression of IM after 8-week celecoxib treatment had a significantly lower COX-2 expression, but not beta-catenin expression, at enrollment than those patients without IM regression (P = 0.031)., Conclusion: Short-term celecoxib treatment can be safe and promising to regress long-term persistent IM after H. pylori eradication.

Background: Helicobacter pylori infection causes chronic gastric inflammation and intestinal metaplasia (IM), related with deregulation of Wnt pathway and over-expressions of COX-2, matrix metalloproteinase (MMP), and tissue inhibitors of matrix metalloproteinase (TIMP). We thus test the host genomic predispositions related to the risk of IM after H. pylori infection., Methods: We enrolled 296 H. pylori-infected patients to provide gastric biopsies for histology and genomic DNA for genotypes of single nucleotide polymorphisms (SNPs), including APC, COX-2, IL-1B, IL-1RN, IL-10, MMP-2, MMP-9, TIMP-1, and TIMP-2 determined by sequence specific oligonucleotide probe, sequence specific primers, restriction fragment length polymorphism, or real-time polymerase chain reaction., Results: There was no association between the presence of IM and SNPs in APC, COX-2, IL-1B, IL-1RN, IL-10, MMP-2, and TIMP-2. The risk of IM was increased up to 2.29-folds in males with TIMP-1 372 C, and 3.03-fold in females with T carrier (p < .05). The combination genotype of MMP-9 -1562/TIMP-1 372 as CC/C and CT/T in males had a 4.5-fold increased risk of IM, as compared to CC/T (p < .05). Females with such combination genotype as CC/T-carrier had a 3-fold risk of IM than males with CC/T (p < .05). In contrast, males' combination genotype as CC/C had a 3-fold risk of IM than females with CC/CC (p = .05)., Conclusions: The host MMP-9 -1562/TIMP-1 372 SNPs had gender differences in the risk of IM after H. pylori infection, and could possibly serve as a host factor to identify the risk group harboring gastric precancerous changes after H. pylori infection.

Objectives: This study aimed to determine whether Helicobacter pylori eradication limits the progression of precancerous changes, manifested as intestinal metaplasia (IM), in patients with reflux esophagitis using long-term esomeprazole., Methods: Three hundred twenty-five reflux esophagitis patients were enrolled and randomly assigned to (i) the H. pylori-positive eradication group receiving 1-week triple therapy (n=105); (ii) H. pylori-positive non-eradication controls (n=105); and (iii) H. pylori-negative controls (n=115). All the patients received continuous esomeprazole until sustained symptomatic response, and when possible, shifted to on-demand therapy (ODT) thereafter. Serial gastroscopy was scheduled on enrollment and at the end of the first and second years to assess the prevalence and progression or regression of gastric atrophy (AT) and IM., Results: There were 93 patients in the H. pylori-eradication group, 83 in the non-eradication controls, and 100 in the negative controls to complete the study. The negative controls had no progression of AT and IM during follow-up. For the H. pylori-positive eradication group, there was significant regression of AT and IM during follow-up (P<0.05). In the H. pylori-positive non-treated controls, the prevalence rates of AT and IM were significantly greater on the second year than on enrollment (P<0.05). During the second-year follow-up, the patients in the eradication group achieved more regression and less development of AT and IM than did the non-eradication controls (P<0.001)., Conclusions: In patients using long-term esomeprazole for reflux esophagitis, screening for and eradicating H. pylori infection are necessary in order to limit the progression or cause the regression of gastric precancerous changes.

Background and Aim: Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first-line or second-line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin-based triple therapy., Methods: The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E-test., Results: The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin-based triple therapy (78.7% vs 10.6%, P < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin-resistant isolates were correlated with a higher incidence of metronidazole resistance (P = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure., Conclusion: The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitor-levofloxacin-amoxicillin may be an alternative choice to serve as the second-line therapy.

Helicobacter pylori eradication can reverse gastric intestinal metaplasia (IM) in some but not all patients. H. pylori induces high levels of nuclear beta-catenin staining in IM tissues, as well as overexpression of cyclooxygenase-2 (COX-2). This study investigated whether the Wnt/beta-catenin pathway plays a role in IM regression following H. pylori eradication. Sixty-five H. pylori-infected patients with IM who had achieved successful H. pylori eradication provided paired gastric samples before and after eradication to analyse the persistence of IM, and to assess COX-2 and nuclear beta-catenin expression. The host genotypes of single nucleotide polymorphisms (SNPs) of the COX-2, beta-catenin (CTNNB1) and adenomatous polyposis coli (APC) genes were analysed. In addition, expression of beta-catenin, E-cadherin and phosphorylated and unphosphorylated glycogen synthase kinase 3beta (GSK-3beta) in cell lines challenged with H. pylori isolates from patients with and without IM persistence was compared by immunoanalysis. After a mean 33.9-month follow-up after H. pylori eradication, 44 patients (67.7%) with IM persistence had a higher rate of high-level nuclear beta-catenin expression in IM tissue than those without IM persistence (P=0.008). The patients with IM persistence had a higher rate of AA, GG and AA APC SNP genotypes at positions 4479, 5268 and 5465, respectively, than the patients without IM persistence (P=0.022). The H. pylori isolates from the patients with IM regression after H. pylori eradication induced more phospho-GSK-3beta in AGS cells than isolates from patients with IM persistence (P=0.011). It is likely that interactions with H. pylori and the patient's Wnt/beta-catenin genetic predisposition determine the outcome of IM persistence following H. pylori eradication.

Background: Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels., Methods: This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney's system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis., Results: Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori-infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p < .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level (p < or = .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori-related gastritis, but positively related to body mass index., Conclusion: There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.

Background: Fluoroquinolone-containing therapy is effective in eradicating Helicobacter pylori. However, the resistance rate of H. pylori to fluoroquinolones in Taiwan has not yet been reported. In this study, we aimed to investigate the susceptibility to antibiotics commonly used in eradication schedules and fluoroquinolones in H. pylori., Methods: A total of 210 clinical isolates of H. pylori were collected from April 1998 to September 2007 from patients in southern Taiwan. The in vitro activities of six antimicrobial agents were determined by the agar dilution method and Etest. The mutations in quinolone resistance-determining regions of gyrA and gyrB were investigated by direct sequencing., Results: Overall, 5.7% of the isolates were resistant to ciprofloxacin and levofloxacin. The resistance rate to amoxicillin, clarithromycin, metronidazole, and tetracycline was 1.0% (two of 210), 9.5% (20 of 210), 27.6% (58 of 210), and 0.5% (one of 210), respectively. The resistance rate to either ciprofloxacin or to levofloxacin increased from 2.8% (1998-2003) to 11.8% (2004-2007). The mutations in gyrA at N87 or D91 had an impact on primary fluoroquinolone resistance in H. pylori. Garenoxacin, but not moxifloxacin, had a good in vitro inhibitory effect against ciprofloxacin/levofloxacin-resistant strains compared with objective minimal inhibitory concentration values., Conclusions: Drug resistance to ciprofloxacin and levofloxacin in H. pylori collected from 2004 to 2007 increased significantly compared with resistance level observed during 1998-2003. The continuous surveillance of quinolone resistance among H. pylori is important in this area.

This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le(b)), x (Le(x)), and sialyl-Lewis x (sialyl-Le(x)) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le(b) intensity over the antrum (p=0.019) but higher Le(b) intensity over the corpus (p=0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le(x) and higher sialyl-Le(x) intensity than those non-infected ones (p<0.05). The H. pylori-infected adults had a higher bacterial density (p=0.004) and Le(b) intensity (p=0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le(b) (p=0.038) and lower Le(x) (p=0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le(b) and had a higher bacterial density than those with weak Le(b) (antrum, p<0.001; corpus, p=0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.

Background and Aims: Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched from active-phase therapy to on-demand esomeprazole as maintenance therapy. Body mass index (BMI) correlates significantly with reflux symptoms. We investigated whether BMI affects the efficacy of esomeprazole in active-phase or subsequent on-demand therapy., Methods: Three hundred fifty patients with RE-AB were prospectively enrolled to receive an 8-wk course of esomeprazole (40 mg/day) as active-phase therapy. Based on the daily severity of acid regurgitation and heartburn, the cumulative proportions of patients with sustained symptomatic response (SSR), defined as free from symptoms for the last 7 days, were compared among different BMI groups (control: BMI <25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI >30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded., Results: SSR rates were lower in both the overweight and obese groups than in the control group (P < 0.001). During on-demand therapy, the mean number of tablets used per 4-wk period was lower in the control group than in either the overweight or the obese group (13.2 vs 15.3 or 16.2, P < 0.05). The failure rate of on-demand therapy increased with increasing BMI-2.4%, 5.3%, and 14.2%, respectively, for the control, overweight, and obese groups (P= 0.002)., Conclusion: For RE-AB, a higher BMI decreases the rate of SSR after 8-wk of esomeprazole therapy, and increases the need for medication and the failure rate of on-demand therapy.

Objective: To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when triple therapy with amoxicillin, clarithromycin, and omeprazole fails., Methods: We investigated 124 patients whose triple therapy including clarithromycin had failed. Clarithromycin resistance was indirectly assessed by the (13)C-urea breath test, with a post-treatment value cut-off point at 15. All patients were randomly divided into two groups, to receive 1-week amoxicillin 1 g and lansoprazole 30 mg twice daily, plus either levofloxacin 500 mg once (ALL-500 group) or twice daily (ALL-1000 group). Six weeks later, the (13)C-urea breath test was repeated to assess whether H. pylori was eradicated., Results: Intention-to-treat (ITT) and per-protocol (PP) analysis showed no difference in H. pylori eradication rates in both the ALL-500 and ALL-1000 groups (ITT: 79% vs. 80.6%, p > .05; PP: 86% vs. 87.5%, p > .05). For both groups, the per-protocol H. pylori eradication rates were also similarly high between patients with a post-treatment value of (13)C-urea breath test < or = 15 and those with a value > 15 (ALL-500: 85% vs. 86.5%, p > .05; ALL-1000: 88.9% vs. 86.8%, p > .05)., Conclusion: One-week levofloxacin 500 mg daily-based triple therapy is effective for eradicating the persistent H. pylori after a failed triple therapy with amoxicillin, clarithromycin, and omeprazole.

Background and Aim: The high cost of the 13C-urea breath test (UBT) limits its wide application for both epidemiological and clinical studies for diagnosing Helicobacter pylori infection. This study examined if a lower-dose UBT, applying 1 mg/kg of bodyweight (maximum 25 mg, UBT(25)), could introduce cost savings while preserving high diagnostic yields for primary H. pylori infection., Methods: Children aged less than 16 years were recruited after obtaining consent. Those children with administration of antibiotics or proton pump inhibitors within 1 month of the tests were excluded. Positive tests for both the UBT with 50 mg urea (UBT(50)) and the H. pylori stool antigen (HpSA) were qualifying criteria for H. pylori infection. Negative results for both indicated non-infection. The UBT(25) was conducted 1 week after the UBT(50). The cut-off points for the UBT(25) ranging from 2delta to 5delta were examined for their sensitivity, specificity and accuracy rates., Results: A total of 153 children were recruited (55% male; mean age 9.1 +/- 3.5 years). Both the UBT(50) and HpSA test were positive in 18 (13.1%) and negative in 119 children, respectively. The sensitivity and specificity of the UBT(25) were optimally achieved at 88.9% (95% confidence interval [CI]: 71.4-100) and 95.0% (95% CI: 91.1-99.9), judged with a cut-off point at 3.5delta. The diagnostic accuracy was significantly higher for children older than 7 years than for those younger than 7 years (98%vs 85%, P = 0.009)., Conclusion: Lower-dose UBT titration by bodyweight can cut costs while maintaining a highly reliable method to screen primary H. pylori infection in children older than 7 years, which is generally beyond school age.

Background/aims: To test the impact of vitamin C supplementation on triple therapy for H. pylori eradication., Methodology: A total of 171 H. pylori-infected patients were randomized to receive different one-week triple therapies, including 20 mg omeprazole, 1 g amoxicillin, plus the following twice daily: (1) 250 mg clarithromycin (C250 group, n=55); (2) 250 mg clarithromycin and 500 mg vitamin C (V-C250 group, n=61); (3) 500 mg clarithromycin (C500 group, n=55). Six weeks after treatment, the success of H. pylori eradication was assessed by a 13C-urea breath test. Each collected H. pylori strain was defined as either clarithromycin susceptible or resistant by E-test., Results: The demographic background, clarithromycin susceptibility of H. pylori, and drug compliance were similar among the three groups (p=NS). For clarithromycin susceptible infection, the V-C250 group had a higher eradication rate than the C250 group (ITT: 85% vs. 68% and PP: 90% vs. 73%, p = 0.03), but had an equivalent rate to the C500 group (p=NS). For clarithromycin resistant infection, all three groups had a similarly poor eradication rate of less than 34%., Conclusions: Adding vitamin C to one-week triple therapy can reduce the dosage of clarithromycin, but preserve the high eradication efficacy for clarithromycin susceptible H. pylori infection.

Aim: To characterize the role of flgK and its protein product in H. pylori colonization., Methods: The PCR cloning method identified the flgK gene. An isogenic flgK mutant was constructed by gene replacement and confirmed by Southern blot analysis and PCR analysis. The recombinant FlgK protein (r-FlgK) was purified. Electron microscopy (EM) was applied to demonstrate the flagella of H. pylori. An in vitro motility test was assessed in semisolid medium. The densities of H. pylori colonization with either the wild-type strain or its flgK mutant were compared among BALB/c mice with or without pre-immunization with r-FlgK. The serological responses to r-FlgK were analyzed for 70 clinical patients with different densities of H. pylori colonization., Results: From a duodenal ulcer strain, the flgK gene was cloned and it contained 1821 bp, with a 95.7% identity to the published sequences. No flagella were observed under EM for the mutant strain, which had a loss of motility. H. pylori density was lower in the BALB/c mice inoculated by the mutant or with pre-immunization with r-FlgK compared to unimmunized mice or mice inoculated by the wild-type strain (P<0.05). In the H. pylori-infected patients, the serological responses to r-FlgK were uniformly low in titer., Conclusion: FlgK encoded by flgK is important for flagella formation and H. pylori motility. Deficiency in FlgK or an enhanced serological response to r-FlgK can interfere with H. pylori colonization. FlgK of H. pylori could be a novel target for vaccination.

Background: The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes., Methods: The study prospectively enrolled 74 Helicobacter pylori-positive gastric cancer patients and 100 H. pylori-positive duodenal ulcer patients to serve as non-cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non-cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Le(a-b-), Le(a-b+), Le(a+b-), and Le(a+b+) subtypes by the anti-Le(a) and anti-Le(b) monoclonal antibodies., Results: These H. pylori-infected patients with gastric cancer had a higher rate of Le(a+b-) phenotype and a lower rate of Le(a-b+) phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P < 0.05). Among these H. pylori-infected patients, the risk of the patients with Le(a+b-) phenotype having gastric cancer was 3.15-fold higher as compared with those with the Le(a-b+) phenotype (P = 0.02, 95% confidence interval: 1.26-7.87). The offspring and cousins of the cancer patients had a higher rate of Le(a+b-) phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non-cancer control (P < 0.05)., Conclusion: Le(a+b-) phenotype of the H. pylori-infected host could be a risk factor (with familial clustering) for gastric carcinogenesis.

Background: Lactobacillus- and Bifidobacterium-containing yogurt (AB-yogurt) can suppress Helicobacter pylori. Improvement of the eradication rate by quadruple therapy of residual H. pylori after failed triple therapy is needed., Objective: We tested whether prior treatment with AB-yogurt improved the efficacy of quadruple therapy in eradicating residual H. pylori after failed triple therapy., Design: One hundred thirty-eight patients in whom triple therapy failed were enrolled for a culture study of H. pylori to assess antimicrobial resistance. These patients were then randomly assigned in equal numbers to either a yogurt-plus-quadruple therapy group or a quadruple therapy-only group. The patients received 1 wk of quadruple therapy with or without a 4-wk pretreatment with AB-yogurt (400 mL/d). In the yogurt-plus-quadruple group, excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were collected before and every 2 wk during the 4-wk ingestion of yogurt. For both groups, a (13)C-urea breath test was conducted > or =6 wk after the quadruple therapy to assess the outcome of residual H. pylori eradication., Results: For the patients in the yogurt-plus-quadruple therapy group infected with either antibiotic-sensitive or -resistant H. pylori, the excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were significantly decreased after the 4-wk ingestion of AB-yogurt (P < 0.0001). The yogurt-plus-quadruple therapy group had a higher H. pylori eradication rate than did the quadruple therapy-only group (intention-to-treat analysis: 85% compared with 71.1%, P < 0.05; per-protocol analysis: 90.8% compared with 76.6%, P < 0.05)., Conclusion: A 4-wk pretreatment with AB-yogurt can decrease H. pylori loads despite antimicrobial resistance, thus improving the efficacy of quadruple therapy in eradicating residual H. pylori.

Objectives: We tested whether the interaction between host gastric Le(x) antigen and the SabA protein of H. pylori determined gastric colonization density., Methods: A total of 145 H. pylori-infected patients were assessed for their bacterial density and gastric Le(b) and sialyl-Le(x) expression. Their corresponding H. pylori isolates were tested for babA2 and sabA genotype by PCR. The sabA-genopositive PCR products were sequenced to check for mutations affecting SabA expression. The BabA and SabA expressions of each isolate were confirmed by Western blotting., Results: All 145 H. pylori isolates were babA2-genopositive and expressed BabA. There were 116 (80%) sabA-genopositive isolates, but only 45 (31%) of the isolates expressed SabA. Sequence of sabA-genopositive PCR products was achieved in 92 isolates, of which 60% had regular CT repeat-pairs and the other 40% had a unique deletion of the CT repeats. Neither the deletion nor the different CT repeat-pairs in the sabA region were totally correlated with SabA expression, defined by Western blotting. H. pylori density was higher in those expressing gastric sialyl-Le(x) antigen (which interacts with SabA) (p < 0.001) only in those patients expressing weak or no gastric Le(b) antigen (which would interact with BabA), not in those with evident expression of gastric Le(b) antigen., Conclusions: In Taiwan, H. pylori isolates are 100% BabA-positive, but only 31% of them express SabA. The interaction between gastric sialyl-Le(x) and SabA of H. pylori determines the colonization density of patients expressing gastric Le(b) weakly or not at all.

Background: Several independent clinical studies have reported that Helicobacter pylori eradication therapy could achieve complete remission in some patients with H. pylori-positive early-stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma., Methods: To compare the long-term results of anti-H. pylori therapy in early-stage, gastric low-grade and high-grade transformed MALT lymphoma, two multicenter prospective studies of anti-H. pylori therapy for early-stage gastric lymphoma conducted in Taiwan, one for low-grade MALT lymphoma, with 34 patients enrolled from March 1996 through April 1999, and one for high-grade transformed tumors (diffuse large B-cell lymphoma with features of MALT, DLBCL[MALT] lymphoma), with 24 patients enrolled since June 1995, were directly compared. In both studies, patients generally received 2 weeks of antibiotics and had multiple sequential follow-up endoscopic examinations until complete histologic remission (CR) or disease progression; patients were monitored through January 31, 2004. CR was defined as regression of lymphoid infiltration to Wotherspoon's score of 2 or less on all pathologic sections of endoscopic biopsy specimens. All statistical tests were two-sided., Results: The H. pylori-positive rate among the 34 low-grade patients was 94% (32 of 34). All 24 selected high-grade patients were H. pylori positive. H. pylori was eradicated in 97% (30 of 31) of evaluable H. pylori-positive low-grade patients and in 92% (22 of 24) of high-grade patients, which led to CR in 80% (24 of 30, 95% confidence interval [CI] = 65% to 95%) and 64% (14 of 22, 95% CI = 42% to 86%) of patients, respectively. None of the five patients who were either initially H. pylori negative or had persistent H. pylori infection after antibiotics achieved CR. After median follow-up of more than 5 years in complete responders, tumor recurrence was observed in three (13%) low-grade patients but not in high-grade patients., Conclusions: Anti-H. pylori therapy may be considered as one of the treatment options for early-stage H. pylori-positive gastric DLBCL(MALT), and large-scale prospective studies to validate its use as first-line therapy for such tumors should be undertaken.

Background and Aim: The causal relationship between Helicobacter pylori infection and recurrent abdominal pain in children is still under debate. This study assessed the relationship between H. pylori infection and recurrent abdominal pain (RAP) in preschool and school children., Methods: A total of 1271 preschool and school children completed a questionnaire to define the RAP or short-term RAP (SRAP) with pain duration from 2 weeks to 3 months. The serum samples of 118 children with RAP, 60 with SRAP and 212 control children without abdominal pain were all tested for anti-H. pylori IgG. Children with abdominal pain and anti-H. pylori seropositivity were followed for 1 year to assess the relationship of H. pylori infection and recurrent abdominal pain., Results: The prevalence rates of RAP and SRAP in children were 9.8% (124/1271) and 5.5% (70/1271), respectively. Children with SRAP had a higher anti-H. pylori seropositive rate than those with RAP (25%vs 5%, P < 0.001) and control (25%vs 9%, P = 0.001). Among children with SRAP, the epigastric pain was related to H. pylori infection (P = 0.002). One year later, 71% (15/21) of the follow-up children (15 with SRAP, six with RAP) became symptom free regardless of the persistence of H. pylori., Conclusion: H. pylori infection is more commonly found in children with short-term RAP, and presentation of epigastric pain in these cases can be considered as a warning alarm to screen for H. pylori infection.

Objective: We tested whether a 13C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori)., Methods: Seventy patients who had failed triple eradication therapy and 108 untreated H. pylori-infected patients were given a 13C-urea breath test, endoscopy for culture of H. pylori, and assessment of clarithromycin resistance. The patients who had failed triple therapy then received 1 week of quadruple therapy to eradicate residual H. pylori., Results: The posttreatment value of the 13C-urea breath test expressed as excessive delta13CO2 per ml (ECR) was higher in patients with residual H. pylori with clarithromycin resistance than in those without (23.8 vs 10.6; P<.0001). With a cutoff of ECR >or< or =15, the 13C-urea breath test was 88.6% sensitive and 88.9% specific in predicting clarithromycin resistance of residual H. pylori. The H. pylori eradication rate of the rescue regimen was higher for patients with a posttreatment ECR of the 13C-urea breath test < or =15 than for those with a value >15 (93.8% vs 73.3%; P<.05). In contrast, in treatment-naive H. pylori-infected patients, the pretreatment value of the 13C-urea breath test did not differ between patients infected with clarithromycin-resistant or-sensitive isolates (P>.05)., Conclusion: The posttreatment value of the 13C-urea breath test is predictive of clarithromycin resistance in residual H. pylori after failed triple therapy and predicts efficacy of the rescue regimen. The value of the noninvasive test is promising for primary care physicians who need to select a rescue regimen without invasive H. pylori culture.

Background: Metronidazole-resistant H. pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (>/= 64 micro g/ml) of metronidazole (Mtz)., Material and Methods: From 126 clinical H. pylori isolates, we examined 14 Mtz-sensitive, 18 Mtz-resistant H. pylori, and eight pairs of Mtz-sensitive and Mtz-resistant colonies simultaneously present within a single gastric biopsy. The paired strains from one single biopsy were proven identical by PCR-RFLP. MICs of Mtz were checked by the E-test and agar dilution method. The mutations of rdxA and frxA sequencing were matched with the Mtz-susceptible ATCC 26695 and J99., Results: There were 89% (16/18) of Mtz-resistant isolates with mutation of RdxA. Half of the 14 Mtz-sensitive strains, all without mutation of RdxA, still contained truncation of FrxA. Within the paired isolates from a single biopsy, rdxA mutation (86%) was more common than frxA mutation (43%) in those isolates with high-level Mtz-resistant H. pylori. RdxA truncation was more prevalent in Mtz-resistant strains with high MICs than in those with low to moderate MICs (75% vs. 20%, p =.01, OR: 12, 95% CI: 1.8-81.7)., Conclusion: Mutations in the rdxA gene rather than the frxA gene generally determine a high MIC level of Mtz-resistant H. pylori in Taiwan.

Background and Aim: Helicobacter pylori infection causes hypergastrinemia. This study aimed to determine the association between serum gastrin and the severity of H. pylori-related gastric histology., Methods: A total of 458 dyspeptic patients were included in this study after the absence of gastric malignancy was confirmed using endoscopy. The gastric specimens of each patient were collected from the antrum and corpus for the analysis of H. pylori-related histology changes by updated Sydney's system. Before endoscopy, the fasting blood samples were collected for gastrin analysis., Results: The H. pylori-infected patients had higher gastrin levels than those without infection (P = 0.01). Gastrin levels were related to H. pylori density and acute and chronic inflammation scores in the corpus mucosa (P < 0.05), but not in the antral mucosa (P = NS). Gastrin levels were also not related to the presence of gastric atrophy. Multivariate regression showed that the gastrin level was only related to acute corpus inflammation. However, in the patients without infection, the gastrin level was also associated with acute corpus inflammation. Nevertheless, the patients with denser H. pylori infection were more likely to have acute corpus gastritis than those with lighter H. pylori infection, and thus presented with higher gastrin levels (P < 0.05)., Conclusions: The increased level of gastrin of serum after H. pylori infection was associated with acute inflammation in the gastric corpus mucosa, but not in the antral mucosa. Denser H. pylori infection causes more severe corpus gastritis and thus may lead to a higher fasting level of gastrin of serum.

Purpose: We tested whether the serological response to Flavodoxin-A (FldA) protein and anti-Helicobacter pylori immunoblots correlated to the degree of mucosaassociated lymphoid tissue (MALT) in the stomach., Methods: Eighty H. pyloni-infected patients with different degrees of MALT in the stomach were investigated with serum sampling and endoscopy on enrolment, the 2nd and the 12th months after anti-H. pylori therapy. All sera were tested for the anti-FldA protein and anti-H. pylon immunoblots, including 19.5, 26.5, 30, 35, 89, and 116 KDa (CagA). Regression of follicular gastritis was assessed by histology., Results: Patients with dense lymphoid follicles had higher prevalence rates of anti-FldA protein, 19.5, 26.5, and 30 KDa antibodies of H. pylori (p < .05). Histologic downgrade of MALT was observed in 25% (10/40) of patients in the 2nd month and in 60% (23/38) in the 12th month after H. pylori therapy. After H. pylori eradication, the patients with MALT and dense lymphoid follicles had significantly negative seroconversions of 19.5, 26.5, 30, and 35 KDa antibodies (p < .05), but not of CagA and FldA., Conclusion: Patients with gastric MALT and dense lymphoid follicles had different anti-H. pylori serological responses to those with scanty or an absence of lymphoid follicles. The negative seroconversion of the smaller-molecular-weight proteins, but not CagA and FldA, may correlate with the regression of MALT by H. pylori eradication.

Purpose: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression., Experimental Design: Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4., Results: H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34-10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001)., Conclusions: GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.

Background/aims: The study aimed to evaluate whether administration of intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding of patients with and without comorbid illness., Methodology: A total of 80 patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and 40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two subgroups were divided, based on the absence (Group A) or presence (Group B) of one or more comorbid illnesses, such as chronic obstructive pulmonary disease, congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke. The 7-day and 28-day rebleeding rates were recorded., Results: The presence of comorbid illness had a higher rebleeding rate than those without comorbid illness (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with two or more comorbid diseases had an even higher risk of rebleeding than those with a single comorbid illness (66.7% vs. 26.5%, p < 0.05)., Conclusions: Low-dose infusion of omeprazole can achieve favorable control of rebleeding in the patients with peptic ulcer bleeding but without comorbid diseases. As patients with comorbid illness had a higher risk of rebleeding, a higher dosage or prolonged duration of omeprazole infusion would be rationally indicated to prevent risk of rebleeding.

Background and Purpose: Reflux esophagitis of Los Angeles grade A or B is more common than grades C and D disease among Taiwanese. This study compared the efficacy of esomeprazole 40 mg and omeprazole 20 mg for starting on-demand therapy for grade A and B reflux esophagitis., Methods: 100 patients with grade A and B reflux esophagitis were randomized to receive either esomeprazole 40 mg once daily (n = 50) or omeprazole 20 mg once daily (n = 50) for the first 4 weeks. Sustained symptomatic response (SSR) was defined as freedom from symptoms for the last 7 days of the 4-week treatment duration. On-demand therapy was used for the next 4 weeks in patients with SSR; patients without SSR continued with the same proton pump inhibitor regimen. Patients were asked to record their daily severity of acid regurgitation (AR) and heartburn (HB). Medication usage during on-demand therapy was recorded., Results: Forty six patients in the esomeprazole group and 45 patients in the omeprazole group completed the study protocol. The rate of SSR was higher in the esomeprazole group than in the omeprazole group (per-protocol: 73.9% vs 51.1%, p < 0.05; intent-to-treat: 68% vs 46%, p < 0.05). The symptomatic scores for AR and HB were similar between patients taking medication continuously and those taking medication on-demand with both esomeprazole and omeprazole. For patients starting on-demand therapy, the total number of tablets used during 4 weeks was lower in the esomeprazole group than in the omeprazole group (13.5 vs 18.5, p < 0.05)., Conclusions: In patients with grade A and B reflux esophagitis, esomeprazole 40 mg was more effective than omeprazole 20 mg for the initiation of on-demand therapy.

Background/aims: This study was designed to test whether c-erb-B2 overexpression can be related to H. pylori infection or clinicohistological characteristics of patients with gastric cancers., Methodology: One hundred patients with gastric cancer were included. Their gastric specimens were evaluated for the presence of H. pylori infection and overexpression of c-erb-B2 on both tumor and non-tumor mucosa. The clinicohistological characteristics, including stage, histological subtype, cell differentiation, and locations of gastric cancer were reviewed., Results: Seventy-five patients (75%) had H. pylori infection. The H. pylori infection rate was higher in the patients with non-cardiac cancers than those with cardiac cancers (87.5% vs. 25%, P < 0.05), higher in the patients with intestinal-type cancers than those with diffuse-type cancers (78.8% vs. 53.3%, P < 0.05). The overexpression of c-erb-B2 on gastric cancers was not significantly different between patients with and without H. pylori infection (30.7% vs. 36%, P = NS). Overexpression of c-erb-B2 on the gastric cancer tissues increased as the tumor stage turned upward (stage I: 10%; II: 23.3%, III: 32.5%, IV: 55%, P < 0.05), and highest in the poorly differentiated cancers (56.6%). Only patients with advanced stages as II to IV had c-erb-B2 overexpression on the non-tumor part of stomach (P < 0.05)., Conclusions: H. pylori infection is closely related with the non-cardiac, intestinal-type gastric cancers, but not with the c-erb-B2 overexpression on the gastric cancer. As c-erb-B2 overexpression on gastric cancer is significantly related with poor tumor differentiation and advanced stage, and it thus implicates a poor prognosis and late event of carcinogenesis.

Background and Purpose: The presence of the cag pathogenicity island (PAI) may enhance the virulence of Helicobacter pylori. This study determined the prevalence of genotypes of the PAI, IS605, and iceA1 in H. pylori strains in Taiwanese and whether these genotypes were related to the type of clinical disease or gastric pathology., Methods: One hundred clinical isolates were collected from 33 duodenal ulcer, 41 nonulcer related dyspepsia, 14 gastric ulcer, and 12 gastric malignancy patients. Polymerase chain reaction (PCR) assays were performed for cagA, cagC, cagE, cagF, and cagN in the cagI region, cagT and orf13 in the cagII region, and IS605 and iceA1 in all H. pylori isolates. Gastric histology of the infected host was reviewed using the updated Sydney system., Results: All strains were positive for all the selected genes in the PAI. PCR amplification found IS605 in 17%, while colony hybridization revealed it in 36% of strains. The prevalence of the cagA gene detected by PCR using cagA1, cagA2, and cagA3 primers was 26, 100, and 100%, respectively. The iceA1 gene existed in 72% of the H. pylori isolates. The mean ulcer size and the severity of acute gastric inflammation in patients infected with iceA1-positive strains were significantly greater than in those infected with iceA1-negative strains (p < 0.05)., Conclusions: All clinical H. pylori isolates from different gastric diseases in our Taiwanese patients were positive for the PAI, but only 36% of these isolates carried an IS605 insertion. The selected genes in the PAI were not correlated with disease outcome. The determination of cagA prevalence is based on the selection of suitable primers. In contrast, bacterial factors such as the presence of iceAl could be related to severity of gastric inflammation and increase in ulcer size in H. pylori-infected patients.