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Background: The expense of the 13C-urea breath test (UBT) to detect Helicobacter pylori infection is mainly due to the cost of 13C-urea and the analysis using isotope ratio mass spectrometry (IRMS). Aim: To test whether a UBT, using a lower dose of urea and lower-priced isotope-selective nondispersive infrared spectrometry (INIS), can preserve diagnostic efficacy in clinical practice. Methods: A total of 177 dyspeptic patients received endoscopy for H. pylori culture and histology. All of them received a UBT in which the duplicate baseline, 10 min, and 15 min breath samples after ingestion of 50 mg 13C-urea were collected to analyse the excess 13CO2/12CO2 ratio (ECR) by IRMS (ABCA, Europa Scientific, UK) and INIS (UBiT-IR200, Photal Otsuka Electronics, Japan), respectively. Results: Of the 177 patients, 84 were infected and 93 were uninfected with H. pylori. A close correlation of ECR was found between IRMS and INIS (r=0.9829 at 10 min; r=0.9918 at 15 min, P

The noninvasive urea breath test (UBT) avoids the discomforts and risks of invasive endoscopic methods of Helicobacter pylori detection. This study investigated the diagnostic efficacy of carbon 13 ((13)C)-labeled UBT for H pylori detection in 70 patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and 70 dyspeptic controls without renal impairment. With H pylori infection defined as a positive result on either histological examination or culture of gastric biopsy specimen, we evaluated the reliability of the (13)C-UBT in detecting H pylori infection in both groups. To ascertain whether HD therapy affects the diagnostic efficacy of the UBT, the test was performed twice in patients with ESRD (before and after HD) at least 72 hours apart. In each UBT session, the baseline, 10-minute, and 15-minute (Delta15) gas samples were obtained to analyze excess (13)CO(2)/(12)CO(2) ratio (ECR). Histological stain and/or culture studies found that 33 of the patients with ESRD (47. 1%) and 42 of the control patients (60%) had H pylori infection. (13)C-UBT for H pylori detection in patients with ESRD was found to be only 93.8% sensitive and 85.3% specific. These results were achieved by gas sampling (Delta15) after HD therapy with a cutoff ECR value greater than 5. Conversely, the UBT in the control group achieved the greatest diagnostic efficacy (sensitivity, 97.6%; specificity, 96.4%) with a comparatively lower ECR cutoff value of 4. We conclude that the diagnostic accuracy for H pylori detection in patients with ESRD could be improved by performing (13)C-UBT (Delta15) after HD therapy and assessing the UBT with a cutoff ECR value greater than 5. However, the diagnostic efficacy of the UBT for patients with ESRD remained less accurate than that for dyspeptic patients without renal impairment.

Background: This study was conducted to determine (1) whether Helicobacter pylori infection decreases in conjunction with time elapsed after gastrectomy and (2) the diagnostic efficacy of 13 C urea breath test (UBT) for H pylori in patients after gastrectomy. Methods: From January 1997 to June 1998, 86 patients who had undergone gastrectomy and 180 patients with dyspepsia without gastrectomy were enrolled. A UBT for the analysis of excess 13 CO 2 / 12 CO 2 ratio (ECR) was obtained for each patient. Each patient also underwent endoscopy to obtain gastric biopsies for histology and H pylori culture. The presence of H pylori by either histology or culture served as the standard to test the efficacy of UBT. The 86 patients with a prior gastrectomy were categorized into 3 subgroups (I, less than 1 year; II, 1 to 3 years; III, greater than 3 years), according to the interval between surgery and UBT. The initial H pylori status of these 86 patients was determined by histologic evaluation of the resected stomach. Results: At trial initiation, the postgastrectomy group had a lower H pylori infection rate (52.3%) as compared with the dyspeptic control group (80%). The initial H pylori status among subgroups I, II, and III was similar. There was a trend for the presence of H pylori in the stomach to decrease with increasing time elapsed after surgery (I to III: 68.8%, 48.3%, 36%, respectively; p Conclusion: The prevalence of H pylori diminishes with time elapsed after gastrectomy. UBT for detection of H pylori is more effective in patients without prior gastrectomy than in patients who have undergone gastrectomy and is less effective than endoscopy for patients who have had a gastrectomy. (Gastrointest Endosc 2000;51:670-5.)

Our objectives were to test the efficacy of [13C] urea breath test (UBT) for H. pylori infection in patients before and after proton pump inhibitor (PPI) based triple therapy, and thus to trace the optimal cutoff value of UBT to monitor H. pylori eradication; and to analyze the histologic bacterial density and distribution of H. pylori in patients with equivocal UBT. A total of 441 dyspeptic cases patients enrolled and completed the study design, including 120 noninfected and 321 H. pylori-infected patients. All 441 cases had received the same protocol of UBT. in which the baseline and 15-min gas samples after ingestion of 100 mg 13C-labeled urea were analyzed for excess 13CO2/12CO2 ratio (ECR). In addition, a first endoscopy was performed in each patient to evaluate the initial status of H. pylori by culture and histology. Of the 321 H. pylori-infected patients, 286 received a second endoscopy and a second UBT six weeks after completing any one of four regimens of the PPI-based triple therapy to document the success of H. pylori eradication. During both sessions of endoscopy, topographic gastric biopsies for histology were sampled to evaluate the distribution and density of H. pylori. Based on the diagnostic standard by culture and histology, the sensitivity and specificity of the first UBT achieved most optimally was 97.5% and 96.7%, respectively, by setting the cutoff point of ECR at 4.0. In contrast, using the same cutoff point of 4.0, the sensitivity and specificity of the second UBT in patients after therapy achieved just 80% and 97.6%, respectively. By applying cutoff points downward of 4.0, 3.5, 3, and 2.5 for the second UBT, the sensitivity was elevated to 80%, 82.8%, 88.6%, and 94.3%, respectively, while the specificity was preserved at more than 95.2%. The overall eradication rate of H. pylori was 87.8% (251/286). Seven of 35 patients with failure of therapy had equivocal ECR at the second UBT (range 2-5), and this accounted for the false negative result. All seven patients had low bacterial densities, and three patients had bacteria distributed only in high body near the cardia. In conclusion, selection of a lower cutoff value of ECR at 2.5 is helpful to maintain the diagnostic accuracy of UBT for monitoring the H. pylori eradication. The equivocal ECR of UBT after therapy would be related to the low bacterial load and its distribution.

The study aimed to examine the serum serological response among H. pylori-infected patients with various upper gastrointestinal diagnoses; to ascertain whether it could be predictive to the diagnostic outcome of dyspepsia. One hundred seventy H. pylori-infected patients with dyspeptic symptoms but without previous treatment were enrolled, including those with duodenal ulcer disease (N = 47), gastric ulcer (N = 23), nonulcer dyspepsia (N = 60), gastric cancer (N = 34), and MALToma (N = 6). Sera from dyspeptic patients without H. pylori infection (N = 33) were used as controls. During endoscopy, gastric biopsies were taken for CLO-test, histology, and culture for the detection of H. pylori infection, defined by a positive culture or positive results of both CLO-test and histology. Total H. pylori IgG antibody was tested by an ELISA method. Antibody responses to specific H. pylori proteins were tested by a western blotting system. Of patients with H. pylori-infected gastroduodenal diseases, 76.5%, 42.9%, 23.6%, 46.7%, 84.1%, 76.5%, 82.9%, and 32.4% on average, showed responses to the 116-kDa (CagA), 89-kDa (VacA), 60-kDa, 45-kDa, 35-kDa, 30-kDa, 26.5-kDa, and 19.5-kDa H. pylori-specific proteins, respectively. A significant association was found between the serological response to 19.5-kDa and 26.5-kDa proteins and malignant outcome of H. pylori infection (P

The amino acid sequences corresponding to the vacA intermediate region from 39 isolates of Helicobacter pylori were investigated. The substitution of a G for the third S in the i1-type cluster B sequence (QASEGIT SSK) conferred a greater risk of gastric diseases (P < 0.03; Fisher’s exact test). The conserved substitutions of an F for the Y in the cluster A sequence and of an M for the second N in the i1-type cluster C sequence could be a marker of VacA in the Taiwanese strains. Helicobacter pylori infects more than 50% of the world’s human population and causes peptic ulcers and gastric malignancy (5). One of the virulence determinants is the vacuolating cytotoxin (VacA) encoded by the vacA gene. The polymorphism of vacA occurs in the signal (s) and mid (m) regions (1). Recently, a new polymorphism, in the intermediate (i) region between the s and m regions, was identified and associated with gastric cancer (12). There are two types of the s (s1 and s2), i (i1 and i2), and m (m1 and m2) regions of vacA (1, 12), and subtypes are also continually being identified (2, 11, 15, 17). Previous reports have shown that the s region affects the vacuolating activity of the toxin in vitro and the m region determines the specificity of toxin binding to host cells (6–8, 10). Rhead et al. (12) further demonstrated that i1-type clusters B (10 amino acids; QAS EGITSSK) and C (10 amino acids; ASNSVKLNGN), but not cluster A (14 amino acids; YKDSADRTTRVDFN), play an important role in the vacuolating activity. The correlation between the vacA genotype and gastric diseases varies across geographic regions. In addition, the distinct dominant vacA genotypes differ among clinical strains from the different geographic regions (11, 15, 16, 18). In Taiwan, there are two specific subtypes in the m region (m1T and chimeric m1Tm2) (17). The sequences of m1T are much more homologous to m1 strains than m2 strains, and several mutations were found in the m1 primer regions. Since Taiwanese isolates have the m1T vacA subtype and gastric cancer is the major leading cause of cancer death in Taiwan (4), it is worth investigating the prevalences of i region types in our clinical isolates and their association with gastric diseases. H. pylori strains were successfully isolated from the biopsy

We aimed to develop an H. pylori-infected mousemodel using clinically stored strains in Taiwan and totest whether development of H. pylori infection in an invivo animal model is related to the status of the cagA gene. A total of 100 male BALB/cmice, 6-8 weeks old, including 80 in the experimentalgroup and 20 in the control group, were used. Twoclinically stored H. pylori isolates, a cagA-positive and a cagA-negative strain, were selected toinduce the H. pylori infection in half (N = 40) of themice in the experimental group. Bacterial isolates of0.8 × 109 CFU/ml were orally inoculatedin each mouse of the experimental group for threeconsecutive days. Ten mice in the control group weresacrificed to confirm the initial absence of H. pylori.Eight weeks after inoculation of the experimental group and no inoculation of the remaining 10mice of the control group, each mouse was killed.Gastrectomy was then performed for rapid urease test(CLOtest) and histology. In the control group, none of 20 mice had positive results from the CLOtestor histology. In contrast, excluding eight of 80 micethat died before the eighth week, 90.3% (65/72) of themice challenged with H. pylori showed persistent presence of H. pylori by histology. Theseverity of gastritis at the eighth week was moreevident in H. pylori-infected mice than in control andnoninfected mice (P 0.05). In summary, storedstrains of H. pylori can be applied to induce aninfection model in BALB/c mice. The less virulentcagA-negative strain can induce H. pylori infection inmice as effectively as the cagA-positive strain. Thehigh prevalence of cagA-positive strains in Taiwanesepatients may be related to factors other than only thecagA gene of the bacteria.

This preliminary study attempted to test whetherpretreatment gastric histology of H. pylori infectionmay affect the success of dual therapy and to identifywhich parameter of gastric histology could be improved after dual therapy. One hundredforty-five dyspeptic patients with H. pylori infectionreceived a two-week course of dual therapy (Amoxicillin500 mg every 6 hr plus omeprazole 20 mg twice a day). In each patient, three pairs of gastricbiopsies, sampled from the antrum, lower body, and upperbody near the cardia, were collected before treatmentand four weeks after completion of dual therapy. The density of H. pylori (score 1-5) and parametersof the modified Sydney system were applied to test theseverity of H. pylori-related gastric histology in eachspecimen. The total bacterial load (score 1-15) was a sum of the density of H. pylorisampled from three biopsies. The overall rate of H.pylori eradication rate by dual therapy is 73.1%(106/145). Univariate analysis of parameters inpretreatment histology disclosed that the presence ofmucosal atrophy (P < 0.01), lymphoid follicles (P< 0.005), and higher-density H. pylori (P < 0.001)predisposed to dual therapy failure. Multivariateanalysis by stepwise logistic regression further confirmed that boththe density of bacteria and the presence of lymphoidfollicles are the two major factors related to theoutcome of dual therapy (P < 0.001). Four weeks after dual therapy was completed, only patients withsuccessful eradication significantly improved in thesegastric histology parameters: acute activity, chronicinflammation, eosinophil infiltration, and mucosal atrophy. However, the lymphoid follicle andintestinal metaplasia were not significantly improvedduring the study period. The eradication rates amongthree subgroups with different total bacterial loads (group I: 1-5; II: 6-10; III: 11-15) discloseda downward trend (I: 89.1%; II: 73%; III: 52.7%). It isconcluded that dual therapy could improve gastrichistology especially among patients with successful eradication of H. pylori. Evaluatingpretreatment histologic parameters, including thedensity of H. pylori and the presence of lymphoidfollicles, is valuable in predicting the success of dualtherapy.

BACKGROUND The incidence of inflammatory bowel disease is increasing worldwide, but data of epidemiological trends from low-endemic area are limited. As one of the low-endemic countries, we describe the trends of this disease in Taiwan over time. METHODS This study was based on data obtained from the Catastrophic Illnesses Registration in the National Health Insurance Research Database, which covers more than 98% of the people in Taiwan. Every certificate of catastrophic illness must be approved by 2 expert gastroenterologists. Thirteen years (1998-2010) of data were analyzed for the trends of Crohn's disease (CD) and ulcerative colitis (UC). RESULTS A total of 2915 incident cases (1818 men and 1097 women) were identified, including 2357 cases of UC and 558 cases of CD. The mean annual incidence rates were 0.80 for UC and 0.19 for CD per 100,000 inhabitants, with lifetime risks for those 20 to 79 years of age of 0.066% and 0.013%, respectively. The mean annual prevalence was 4.59 for UC and 1.05 for CD per 100,000 inhabitants. Poisson regression showed significantly increased trends during the observation period for both diseases, with a men/women ratio of 1.50 in UC and 2.14 in CD (P < 0.01). The mean age of individuals at diagnosis was higher for UC as compared with CD (44.7 versus 37.9, P < 0.001). CONCLUSIONS Inflammatory bowel diseases are still relatively uncommon in Taiwan, but the incidence and prevalence rates are increasing.

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.

Patients with hypoalbuminemia have an increased risk of ulcer rebleeding and longer length of hospitalization. This study aimed to test whether intravenous albumin can decrease the incidence of rebleeding or shorten the duration of hospitalization in patients with bleeding peptic ulcers and hypoalbuminemia. Sixty-two patients with bleeding peptic ulcers and Rockall scores ≥6 were prospectively enrolled after having received endoscopic therapy. The enrolled patients were divided into a normal albumin group (serum albumin ≥3 g/dL, n = 39) or an intervention group (

Summary Background To eradicate Helicobacter pylori before the occurrence of precancerous changes is important to prevent gastric carcinogenesis. Aim To validate whether the corpus-predominant gastritis index (CGI) can serve as an early marker to identify the H. pylori-infected patients at risk of gastric carcinogenesis. Methods This study enrolled 188 subjects, including 43 noncardiac gastric cancer patients, 63 of their first-degree relatives and 82 sex- and age-matched duodenal ulcer patients as controls. All received endoscopy to provide topographic gastric specimens to test for H. pylori infection and its related histological features, translated into the operative link on gastritis assessment (OLGA), operative link on gastric intestinal metaplasia assessment (OLGIM) stages, and the presence of CGI. Spasmolytic polypeptide-expressing metaplasia (SPEM) was assessed by immunohistochemistry staining of trefoil factor 2. Results Gastric cancer patients had higher prevalence of CGI and OLGIM stage II–IV, but not OLGA stage II–IV, than the controls (P = 0.001, OR = 3.4[95% CI: 1.4–8.1] for CGI; OR = 5.0[95% CI: 2.0–12.8] for OLGIM). In patients with the combined presence of CGI and OLGIM stage II–IV, the risk of gastric cancer increased to 9.8 (P

Background: We studied whether different initial bacterial densities of Helicobacter pylori would alter the eradication rate of H. pylori by triple therapy (amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. for 14 days; bismuth subcitrate 120 mg t.i.d. for 28 days) in patients with duodenal ulcer bleeding. Method: One hundred thirty-six cases with duodenal ulcer bleeding and H. pylori infection (proved by rapid urease test and histology during emergency endoscopy) were studied. One hundred twenty-seven of these patients completed a course of triple therapy. In each case, anti- H. pylori IgG titer, gastric biopsies for H. pylori density (score 1 to 5), and evaluation of severity of gastritis were collected at the first endoscopy and 1 month after completion of the triple therapy. Results: The ulcer healing rate was 84.3% (107 of 127) at the time of the second evaluation. The eradication rate of H. pylori was 76.4% (97 of 127). Eradication for H. pylori failed in 30 cases. In these eradication failure cases, initial serologic titer and density of H. pylori were higher than those of eradication success cases. The eradication rate of H. pylori decreased as the initial density of H. pylori increased (density of H. pylori: 1, 88.3%; 2, 83.8%; 3, 74.2%; 4, 68%; 5, 50%). At the second evaluation, the serologic titer was lower and continued to decline in eradication success cases whose mean residual titer ratio (100% × follow-up titer / initial titer) was lower than that of eradication failure cases (57.1% ± 14.6% vs 107.1% ± 24.1%, p H. pylori increased (density of H. pylori 1 to 5: 57.5%, 66.6%, 73.5%, 75.3%, 81.8%, respectively). Conclusions: We suggest routine gastric biopsy to detect both the presence of H. pylori and its density inasmuch as quantitative results may predict the usefulness of triple therapy. The higher the H. pylori density, the less effective triple therapy will be at successful eradication of H. pylori . (Gastrointest Endosc 1996;44:683-8.)

Question Does treating H. Pylori reduce the incidence of gastric cancer? Study Randomised placebo-controlled trial. Main results At 7.5 years, incidence of gastric cancer was not significantly different between groups (treatment: 0.86%, n= 7; placebo: 1.35%, n =11; p =0.33). In people without precancerous lesions at baseline, risk of gastric cancer was significantly lower for treatment compared with placebo (incidence of gastric cancer: treatment n =0; placebo n =6; p =0.02) but there was no difference among people with precancerous lesions ( n =7 and 5, respectively). Smoking (hazard ratio [HR] 6.2, 95% CI 2.3 to 16.5) and older age (HR per 1 year 1.10, 95% CI 1.05 to 1.15) were independent predictors of gastric cancer risk. Authors’ conclusions Incidence of gastric cancer was similar between H. pylori eradication and placebo groups over 7.5 years of follow-up. However, it was significantly reduced in a subgroup of people without precancerous lesions at baseline.

The suprahepatic region is a rare ectopic location of the gallbladder. It usually combines with right lobe anomaly of the liver. Here we report two unusual cases of suprahepatic gallbladder with agenesis or hypogenesis of the right lobe of the liver and biliary cancer. A patient with a gallbladder tumor was admitted to our emergency room with acute cholecystitis and liver abscess. Imagining examinations and operation confirmed the suprahepatic position of gallbladder, agenesis of the right lobe, and dissemination of gallbladder cancer. In the patient with cholangiocarcinoma, CT scans and percutaneous transhepatic cholangiography documented the presence of a hilar tumor and hypogenesis of the right lobe. Both of these patients died from biliary tract cancer soon after operation.

Background Motility mediated by the flagella of Helicobacter pylori is important for the cells to move toward the gastric mucus in niches adjacent to the epithelium; then, H. pylori uses the adhesin SabA to interact with sialyl-Lex on inflammatory host cells for persistent infection. Here, we reveal the clinical association of bacterial motility, SabA expression, and pathological outcomes. Methods Ninety-six clinical isolates were screened for bacterial motility, and the expression of SabA of each isolate was confirmed by Western blotting. H. pylori-infected patients were assessed for their bacterial density, sialyl-Lex expression, inflammatory scores, and clinical diseases. Results The mean diameter in the motility assay was 17 mm, and eight (8.3%) of the strains had impaired motility, with a diameter

Background. Two major causes of gastric ulcers areHelicobacter 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) betweenH. pylori-infected and NSAID-related ulcers.Methods. The 126 gastric ulcer patients (H. pyloriinfectedn=46; NSAID relatedn=30; combined with two factorsn=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 thanH. 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 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 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 vs. 9.7%, p p 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 Conclusions The H. pylori isolate with the AB AB genotype correlates with an increased gastric cancer risk, and colonize in an antrum predominant manner.

Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.

Matrix metalloproteinases (MMPs) are elevated in patients with squamous cell carcinoma (SCC) over either the head and neck (HNSCC) or the esophagus (ESCC). Synchronous SCC with both HNSCC and ESCC predispose to worse survival. This study tested if serum MMP levels correlate with clinical features and predict survival for HNSCC, ESCC, and synchronous SCC. One hundred and thirty patients with SCCs in upper aero-digestive tract (70 ESCC, 20 HNSCC, and 40 synchronous SCC) and 74 healthy controls were assessed for serum MMP-3, -7, and -9 titers by enzyme-linked immunosorbent assay. The titers were validated to their correlations to clinical features and survival rates of the different SCC groups. Patients with SCCs had significantly higher serum MMP-3, -7, and -9 titers than the controls (P0.001) but there was no difference among the three SCC groups. Based on the optimal MMP cut-off values by ROC curve, elevated MMP-3 and MMP-9, but not MMP-7, correlated with distant metastasis and poor survival (P0.05). Concomitantly elevated MMP-3 (14 ng/mL) and MMP-9 (329.3 ng/mL) independently correlated with poor two-year survival (P = 0.002, by log rank test). Cox regression confirmed that such concomitant elevation was superior to the tumor stage of either ESCC or HNSCC in predicting survival for synchronous SCC. Serum MMPs are elevated in SCC of the upper aero-digestive tract. Especially for synchronous SCC, concomitantly elevated MMP-3 and MMP-9 levels serve as better biomarkers to predict prognosis than TNM staging of ESCC or HNSCC.

The present study determined whether the genotypes of S-mephenytoin 4'-hydroxylase (CYP2C19) could serve as an indicator to assess the success of long-term on-demand therapy (ODT) with pantoprazole for the patients with severe reflux esophagitis as Los Angles grade C or D (RE-CD).A total of 240 patients with RE-CD were prospectively enrolled to receive continuous pantoprazole, 40 mg daily for 6 months. The patients, who achieved complete healing and were free from acid reflux-related symptoms during follow up, were included to receive ODT with a 40 mg pantoprazole tablet up to 1 year. Each patient was followed to assess the monthly tablet number of 40 mg pantoprazole and the cumulative rate of failure of ODT. The CYP2C19 genotype of each included patient was defined as homologous extensive metabolizer (HomoEM), heterologous extensive metabolizer (HeteroEM), and poor metabolizer (PM).Two-hundred patients were included to receive ODT, including 51 as HomoEM, 108 as HeteroEM, and 41 as PM. There were no differences in demographic and endoscopic features among patients with different CYP2C19 genotypes (P0.05). The 1-year cumulative failure rate of ODT was significantly higher in HomoEM than in HeteroEM and PM (P0.05, by log-rank test). For those with successful ODT during the 1-year follow up, the mean monthly tablet number of pantoprazole was lower in PM than in HeteroEM and HomoEM (11.5 vs 16.3 and 18.6, P0.05).For RE-CD with complete healing after continuous pantoprazole, the successful shift to ODT is determined by the CYP2C19 genotypes of the patients.

Background Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area. Results We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the H. pylori isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by in vitro AGS cells co-culture. The p-CagA was sparse in 30 (20.5%), weak in 59 (40.5%), and strong in 57 (39%) isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (p ≤ 0.002). Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (p < 0.05, odds ratio 3.09~15.26) than those infected with sparse p-CagA isolates. Conclusions Infection with H. pylori stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer.

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).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.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).Increased gastric OPN expression by H. pylori infection can correlate with a more severe gastric inflammation and the presence of IM.

There is a growing body of evidence supporting the concept that inflammation plays an important role in the initiation and progression of atherosclerosis and its complications.1,2 Previous studies 1,3 have demonstrated that there are infectious and noninfectious factors that may drive the inflammatory activities in coronary artery disease (CAD). Helicobacter pylori (H. pylori) is a gram-negative, flagellate bacillus that is associated with peptic ulcer disease and gastric malignancy.4 The relation between H. pylori infection and CAD has been studied extensively.5‐ 8 Nevertheless, the effect of H. pylori infection on the long-term outcome of patients with CAD remains unknown. Because serum level of specific anti-H. pylori immunoglobulin G (anti-H. pylori IgG) antibody is a reliable indicator of chronic H. pylori infection,9,10 we evaluated the serum concentrations of anti-H. pylori IgG antibody among patients with CAD in this study to determine whether H. pylori infection was a predictor for subsequent ischemic events during followup. ••• Ninety consecutive patients admitted to our hospital with a diagnosis of CAD were included in this study. All patients underwent coronary angiography and had coronary stenosis .50% in diameter in $1 major coronary artery. After admission, these patients received appropriate treatment, including percutaneous transluminal coronary angioplasty (n 5 30), coronary bypass surgery (n 5 30), or medication only (n 5 30). Of these patients, 4 were excluded because 1 patient died during bypass surgery and 3 patients were lost to follow-up. The remaining 86 patients (mean age 62 years; 64 men) formed the basis of this study. No patients had peptic ulcer disease, uremia, and any previous coronary intervention or bypass surgery. According to the World Health Organization diagnostic criteria, 48 patients had a previous myocardial infarction. The 86 patients were free of ischemic symptoms when discharged from our hospital and regularly followed in our cardiology clinic after discharge. The study end points were acute myocardial infarction, or hospital readmission due to newly developed class III or IV angina according to Canadian Cardiovascular Society classification. Blood samples were drawn after fasting overnight and before catheterization for anti-H. pylori IgG antibody study. The blood samples were centrifuged at 1,000 g for 10 minutes. The supernatant serum was collected and immediately frozen at 270°C until analyzed. Serum assay for specific anti-H. pylori IgG antibody was performed using a highly sensitive and specific enzyme-linked immunosorbent assay (HEL-p test, Amrad Corporation, Victoria, Australia). The IgG assay had both a sensitivity and specificity of .90%. 11,12 All patients were divided into 2 groups according to the occurrence or nonoccurrence of new ischemic events. Levels of anti-H. pylori IgG antibody, clinical characteristics, and management were compared between patients with or without ischemic events. Chisquare tests were used for categorical variables, and Student’s t tests were used for continuous variables. Pearson’s correlation analysis was used to assess the relation between levels of anti-H. pylori IgG antibody and patients’ age, concentrations of serum lipoproteins, C-reactive proteins, and left ventricular ejection fraction. A Cox proportional hazard model was used for analysis of the risk factors for ischemic events. The data for levels of anti-H. pylori IgG antibody

We tested whether cagL amino acid sequence polymorphisms of Helicobacter pylori correlated to clinico-histological outcomes and gastric α5β1 integrin expressions. One hundred forty five patients with H. pylori infection and 47 noninfected controls were enrolled to check gastric integrin α5β1 intensities topographically. The collected isolates were screened for cagL-genotype by polymerase chain reaction (PCR), and assessed for amino acid sequence polymorphisms using sequence translation. Our H. pylori isolates were predominantly (98.6%) cagL-genopositive, 95.8% of which had the RGD motif in their amino acid sequences. The isolates from the gastric cancer (GCA) patients indicated a higher rate of amino acid sequence polymorphisms-Y58 and E59-than those of the non-GCA patients (P 0.05). The polymorphisms as Y58E59 noted with increased risk of GCA up to 4.6-fold (95%CI: 1.8-11.9). H. pylori-infected patients had higher integrin α5β1 than noninfected patients (P 0.05). Furthermore, cagL-Y58E59 H. pylori infection predisposed an upward shift in integrin α5β1 (P = 0.007) in the corpus, leading to more severe corpus chronic inflammation (P 0.05). H. pylori CagL amino acid polymorphisms like Y58E59 correlate with a higher risk of GCA, and may regulate a corpus shift of gastric integrin α5β1 to lead to severe corpus gastritis during gastric carcinogenesis.

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 We performed an assessment of an independent rapid flu clinic service (RFCS) unit, which was set up outside the emergency department (ED) during the 2009 H1N1 pandemic season. The unit was able to relieve the crowding of regular ambulatory and emergency services. Methods Between August and December 2009, a total of 6,152 patients with influenza-like illness were enrolled in this observational retrospective study. Patients with positive influenza tests were interviewed to evaluate the efficiency of RFCS. Results The mean length of stay (LOS) for the RFCS was 50 minutes, which was shorter than the LOS for ambulatory services (1 hour) and regular ED services (3.5 hours). Overall, 88% of patients were satisfied with the RFCS. Of 6,152 patients receiving flu tests, 1,235 (20%) had a positive result. Fever (odds ratio [OR], 4.28, 95% confidence interval [CI]: 3.11-5.89), fever combined with cough and sore throat (OR, 2.52; 95% CI: 2.18-2.92), fever combined with sore throat (OR, 2.42; 95% CI: 2.13-2.75), history of contacting confirmed flu patients within 7 days (OR, 2.40; 95% CI: 2.07-2.78), fever combined with cough (OR, 2.19; 95% CI: 1.92-2.47), sore throat (OR, 2.03, 95% CI: 1.79-2.30); and cough (OR, 1.91, 95% CI: 1.69-2.17) were significantly associated with positive influenza tests. Conclusion Setting up the RFSC was beneficial to health care facilities during a pandemic flu season.

We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles (LA) classification in defining the severity of erosive reflux esophagitis (RE) and predicting the treatment response by esomeprazole.Five hundred twenty-four subjects (424 RE and 100 controls) with normal body mass index and hemoglobin had undergone endoscopy to confirm the RE grade by LA classification and to check the series of IHb values at every centimeter of the esophageal mucosa while withdrawing the endoscope to above the esophageal-gastric junction (EGJ). The RE cases had received esomeprazole for 8 weeks (40 mg/day) to assess the cumulative proportions of sustained symptomatic response (SSR).The IHb value at the EGJ was higher in RE patients than in controls (P0.001). Selecting 70 as the cutoff IHb value at the EGJ, the efficacy to define RE achieved 95.8% (406/424) sensitivity and 94% (94/100) specificity. For the patients with same the LA grade, the length of IHb value70 above the EGJ (L-IHb70) that is greater than 4 cm correlated with a poor cumulative rate of SSR (P0.01).The IHb value70 at the EGJ is a reliable indicator of RE. The L-IHb70 can serve as a supplementary indicator to predict the response to esomeprazole index within the same LA grade.

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/Purpose: Peptic ulcer disease (PUD) in children is relatively rare as compared with adults. This study aimed to assess the etiology, clinical and histological characteristics, and treatment of PUD in children. Methods: All children aged ＜ 18 years with an endoscopic diagnosis of PUD were enrolled in a tertiary referral center. The demographic data, clinical, endoscopic, and histological findings were compared between patients with different causes of PUD. Results: From 1234 endoscopic examinations, 67 (5.4%) children (median age, 11.4 years) with gastric ulcer (GU; n=27) or duodenal ulcer (DU; n=40) were included. Thirty-two (47.7%) of them had Helicobacter pylori infection and 11 (16.5%) had previous use of non-steroidal anti-inflammatory drugs (NSAIDs). Non-H. pylori, non-NSAID PUD was found in 24 (35.8%) patients. Children with H. pylori-related PUD had a significantly higher mean age, antral chronic inflammatory score, rate of familial PUD, and presence of DU and nodular gastritis than those with NSAID-related and non-H. pylori, non-NSAID PUD (p＜0.01). In contrast, children with NSAID-related PUD had a higher rate of upper gastrointestinal bleeding, associated with acute febrile disease, than those with H. pylori-related and non-H. pylori, non-NSAID PUD (p＜0.05). All but two patients with non-H. pylori, non-NSAID PUD were disease free after H. pylori eradication and proton pump inhibitor treatment for 1-2 months. Conclusion: In children, H. pylori-related PUD is associated with familial peptic ulcer and the presence of DU. However, short-term NSAID use is correlated highly with GU. The outcome of childhood PUD is good.

Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustained symptomatic response (SSR) to proton pump inhibitors for patients with reflux esophagitis of Los Angeles grade A or B (RE-AB). We thus investigated whether double-dosed pantoprazole can accelerate SSR in such patients.A total of 200 overweight or obese patients with RE-AB were evenly randomized into a double-dosed group (receiving 8-week pantoprazole 40 mg twice daily) or a standard-dosed control group (receiving 8-week pantoprazole 40 mg per day and one blank tablet at night). In each patient, demographic factors and the genotype of S-mephenytoin 4'-hydroxylase (CYP2C19) were checked and defined as poor metabolizer (PM), or homologous extensive metabolizer (HomoEM), or heterologous extensive metabolizer (HeteroEM). The cumulative proportions of patients with SSR were compared during the 8-week period.Both intention-to-treat and per-protocol analyses disclosed that the rates of SSR were higher in the double-dosed group than in the standard-dosed group from week 4 (P=0.005) until week 8 (P=0.01). While using standard-dosed pantoprazole, PMs had better rates of SSR during the 8-week period than both HomoEMs and HeteroEMs (P0.05). By using double-dosed pantoprazole, the cumulative rates of SSR were improved as early as week 4 for both HomoEMs and HeteroEMs (P0.005, log-rank test).For RE-AB in overweight and obese patients, double-dosed pantoprazole effectively accelerates the SSR, especially for those with CYP2C19 genotypes as HeteroEM or HomoEM. Accordingly, it offers an earlier shift into on-demand pantoprazole for RE-AB patients with high BMI.

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

Background and Aim: The intestinal metaplasia (IM) has overexpressions of cyclooxygenase-2 (COX-2) and β-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 β-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 β-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.

Peristomal infection is common after percutaneous endoscopic gastrostomy. This study aims to evaluate the correlation between airway and peristomal infected pathogens.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.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, p0.001). 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.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.

Helicobacter pylori eradication can reverse gastric intestinal metaplasia (IM) in some but not all patients. H. pylori induces high levels of nuclear β-catenin staining in IM tissues, as well as overexpression of cyclooxygenase-2 (COX-2). This study investigated whether the Wnt/β-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 β-catenin expression. The host genotypes of single nucleotide polymorphisms (SNPs) of the COX-2, β-catenin (CTNNB1) and adenomatous polyposis coli (APC) genes were analysed. In addition, expression of β-catenin, E-cadherin and phosphorylated and unphosphorylated glycogen synthase kinase 3β (GSK-3β) 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 β-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-3β 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/β-catenin genetic predisposition determine the outcome of IM persistence following H. pylori eradication.

This study presents a computer-aided diagnosis system using sequential forward floating selection (SFFS) with support vector machine (SVM) to diagnose gastric histology of Helicobacter pylori (H. pylori) from endoscopic images. To achieve this goal, candidate image features associated with clinical symptoms are extracted from endoscopic images. With these candidate features, the SFFS method is applied to select feature subsets, which perform the best classification results under SVM with respect to different histological features. By using the classifiers obtained from the feature subsets, a new diagnosis system is implemented to provide physicians with H. pylori -related histological results from endoscopic images.

Long-term surveillance of pyogenic liver abscess remains unavailable. We thus aimed to identify the recurrence rates of pyogenic liver abscess among various etiologies and pathogens, and to elucidate the factors related with this recurrence.Six-hundred and one patients with pyogenic liver abscess were prospectively enrolled to observe abscess recurrence during a mean follow-up period of up to 6.06 years. On the basis of the etiology of the initial abscess, patients were divided into different subgroups as follows: there were 152 (25.3%) patients classified as cryptogenic, 229 (38.1%) with diabetes mellitus, 144 (24%) with underlying biliary tract disease, and 76 (12.6%) with other organic diseases or mixed subgroups.The cumulative recurrence rates of pyogenic liver abscess were lower in both the cryptogenic (2.0%) and diabetic (4.4%) groups than in the underlying biliary tract disease (23.8%) group (log-rank test, P0.001). The diabetic group had a higher rate of Klebsiella pneumoniae infection and a lower rate of Escherichia coli infection than the biliary tract group (P0.001). For patients infected with K. pneumoniae, the recurrence rate of pyogenic liver abscess was as low as that of the diabetes and the cryptogenic groups (P0.05).Pyogenic liver abscess is more commonly recurrent in patients with underlying biliary tract disease. Irrespective of diabetic status or cryptogenic etiology, the recurrence of K. pneumoniae-infected liver abscess is low in the long-term.

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.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: BMI25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI30 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.SSR rates were lower in both the overweight and obese groups than in the control group (P0.001). 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, P0.05). 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).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.

To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when triple therapy with amoxicillin, clarithromycin, and omeprazole fails.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.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 testor = 15 and those with a value15 (ALL-500: 85% vs. 86.5%, p.05; ALL-1000: 88.9% vs. 86.8%, p.05).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.

To test the impact of vitamin C supplementation on triple therapy for H. pylori eradication.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.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%.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.

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.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.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).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.

To characterize the role of flgK and its protein product in H. pylori colonization.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.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 (P0.05). In the H. pylori-infected patients, the serological responses to r-FlgK were uniformly low in titer.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 Lea–b–, Lea–b+, Lea+b–, and Lea+b+ subtypes by the anti-Lea and anti-Leb monoclonal antibodies. Results: These H. pylori-infected patients with gastric cancer had a higher rate of Lea+b– phenotype and a lower rate of Lea–b+ phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P

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.

This study aimed to evaluate whether (1) the portal venous flow pattern determined by color Doppler sonography could be related to the clinical severity of liver cirrhosis and (2) whether the flow patterns differ between patients with bleeding and nonbleeding esophageal varices. One hundred twenty-nine cirrhotic patients and 60 noncirrhotic healthy controls were enrolled after endoscopic survey for the presence of esophageal varices. Each patient received color Doppler echography to define the pattern of blood flow direction as hepatopetal or nonhepatopetal (hepatofugal, turbulence, and bidirection) in type. The patients with esophageal varices were further categorized into two groups: with recent bleeding (BEV; n = 99) and without recent bleeding (NBEV; n = 30). More patients in the BEV group (72.7%) had a nonhepatopetal Doppler flow pattern than in the control group (1.7%) and NBEV group (13.3%) (P < 0.001). Among the 129 cirrhotic patients, the nonhepatopetal flow pattern of the portal vein was higher in 96% of Child-Pugh grade C patients than in 41.8% of grade A patients and 57.6% of grade B patients (P < 0.05). Moreover, for those cirrhotic patients with Child-Pugh grades A and B, the nonhepatopetal Doppler flow pattern was more commonly found in the BEV group than in the NBEV group (63.0 vs. 13.8%; odds ratio, 10.64; 95% CI, 0.03-0.299; P < 0.001). Portal venous blood flow pattern is related to severity of cirrhosis. The presence of a nonhepatopetal flow pattern implicates an increased risk of esophageal varices bleeding, especially for those cirrhotic patients with Child-Pugh grades A and B.