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

H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7–14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p

This study investigated whether levofloxacin-containing concomitant therapy can effectively eradicate Helicobacter pylori infection in patients with type 2 diabetes mellitus (T2DM).A total of 797 T2DM patients were screened for anti-H. pylori IgG antibodies, and the presence of H. pylori infection was confirmed byThe H. pylori eradication rates with concomitant therapy were higher than sequential therapy in both intention-to-treat (96.4% versus 81.4%, p = 0.012) and per-protocol (100% versus 85.4%, p = 0.006) analysis. The adverse effects in both groups were similarly mild. In the patients who received sequential therapy, clarithromycin resistance was significantly associated with eradication failure (p = 0.02). There were no significant differences in the antibiotic-resistant rates to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin between the patients with and without T2DM.Ten days of levofloxacin-containing concomitant therapy is an effective and well-tolerated treatment to eradicate H. pylori infection for T2DM patients. Key messages Ten days of levofloxacin-containing concomitant therapy is well tolerated and superior to clarithromycin-containing sequential therapy for first-line H. pylori eradication in patients with type 2 diabetes. Clarithromycin resistance to H. pylori is the main factor associated with eradication failure in clarithromycin-containing sequential therapy in diabetic patients.

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

Background: H. pylori infection with triple-drug resistance to clarithromycin, metronidazole, and levofloxacin (TR) limits the success of rescue therapy. This study identified the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. Methods: We consecutively enrolled 430 patients with at least one-course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with a positive 13C-urea breath test after the 1st rescue therapy were retreated with a cross-over 2nd rescue therapy. Findings: The MTBP regimen had higher eradication success than the ATBP regimen for the 1st rescue therapy of TRH. pylori (intent-to-treat [ITT] analysis: 70.3 vs. 46.9%, p=0.048; per protocol [PP] analysis: 78.8% vs. 51.7%, p=0.025). For the MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p

Accession numbers of htrA gene analyzed in this study. (DOCX 37 kb)

Background/Purpose Helicobacter pylori is a human gastric pathogen. Antibiotic resistance of H. pylori has become a problem increasing the failure of H. pylori eradication. Therefore alternative approaches are required. The aim of this study was to evaluate the anti- H. pylori activity of Lactobacillus pentosus strain LPS16 and the mechanism of its killing effect. Methods The anti- H. pylori activity of LPS16 was determined by the disc diffusion test and time killing assay. High-performance liquid chromatography analysis was used to analyze the secreted compounds of LPS16. Sixty H. pylori strains isolated from different gastric diseases, having different antibiotic susceptibility were collected to analyze the spectrum of anti- H. pylori activity of LPS16. Adhesion ability of LPS16 to gastric epithelial cell lines was assayed by flow cytometry. Results The anti- H. pylori activity of LPS16 depended on the secreted component, and lactic acid mediated bactericidal activity against H. pylori . The bactericidal activity did not vary significantly among the strains isolated from different diseases having different antibiotic susceptibility. Moreover, LPS16 can adhere on gastric epithelial cell lines AKG and MKN45. Conclusion L. pentosus strain LPS16 had the broad-spectrum anti- H. pylori activity, suggesting that it can be used to prevent H. pylori infection.

Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P

Background and Aim We assessed the feasibility of combined endoscopic ultrasound and computed tomography on response evaluation in patients with esophageal squamous cell carcinoma treated by definitive chemoradiotherapy, and the impact of response on prognosis. Methods Sixty patients treated by definitive chemoradiotherapy were followed by miniprobe endoscopic ultrasound and computed tomography. The post-treatment esophageal wall thickness was measured by miniprobe endoscopic ultrasound. Metastatic tumors were evaluated by computed tomography. The correlation between post-treatment image findings and prognosis was evaluated. Results Twenty-four patients (40%) had esophageal stricture after chemoradiotherapy, which limited complete evaluation by endoscopy. Miniprobe successfully penetrated all strictures to measure post-treatment esophageal wall thickness. Both post-treatment esophageal wall thickness 30 months, 16.8 months and 7.1 months, respectively (P

BACKGROUND Tolerance to the early acquisition of Helicobacter pylori is suggested because of a biased ratio of regulatory to effector T cells in a mice model. This study investigated whether the CD4CD25 regulatory T (Treg) and CD4+CD25- effector T (Teff) cell responses after H. pylori exposure determine H. pylori susceptibility in children. METHODS Treg and Teff cells from peripheral blood mononuclear cells (PBMCs) of H. pylori-infected and non-infected children were incubated with H. pylori protein. The cytokine levels and fraction of FOXP3+ to T cells were measured. FOXP3 expression was assessed by Western blotting and immunohistochemistry of gastric biopsies from dyspeptic children. RESULTS The fraction of FOXP3+ to CD4+CD25 high cells in PBMCs, FOXP3-positive staining and translation level in gastric tissues were higher in H. pylori-infected children than in controls (P < 0.05). The translation levels of TGF-β1 in gastric tissues were higher in H. pylori-infected children than in controls (P < 0.05). After H. pylori challenge, H. pylori-infected children had a positive net-change in TGF-β1 from Treg cells, and a negative net-change of IFN-γ from Teff cells. Paradoxically, the non-infected controls had a negative net-change in TGF-β1 from Treg cells, and a positive net-change of IFN-γ from Teff cells. CONCLUSIONS The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to H. pylori susceptibility in children.

Background Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. Methods A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. Results The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p

Background Corpus-predominant gastritis index (CGI) is an early histological marker to identify Helicobacter pylori-infected gastric cancer relatives at risk of cancer. This study validated whether CGI is more prevalent in H. pylori-infected nonulcer dyspepsia (NUD) subjects than in duodenal ulcer (DU) controls and whether it is reversible after H. pylori eradication or is correlated with noninvasive biomarkers. Materials and Methods In this longitudinal cohort study, 573 H. pylori-infected subjects were enrolled, including 349 NUD and 224 DU. Gastric specimens were provided to assess CGI, spasmolyic polypeptide-expressing metaplasia (SPEM), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM). Serum pepsinogen I and II levels were assessed using enzyme-linked immunosorbent assay. CGI subjected were followed up at least 1 year after H. pylori eradication. Results NUD subjects had higher prevalence rates of CGI (47.0% vs 29.9%, P

BACKGROUND AND AIMS Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication. METHODS We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication. RESULTS GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P

Summary Introduction As a rule, diverticulosis of the appendix is identified incidentally during a pathological examination after an appendectomy. The disease is rare and easily ignored. Only one case has been reported in Taiwan. Aim In this study, we retrospectively reviewed the medical records of patients who had undergone appendectomy at the Ton Yen General Hospital, a local hospital in Taiwan. Methods From June 2004 to May 2012, 10 patients with appendiceal diverticulosis were documented. Their clinical presentations, laboratory data, and pathological characteristics were analyzed. Results All patients were diagnosed after their operations. The incidence rate was 0.88% (10/1131). The patients comprised eight men and two women. The age distribution was 22–71 years with an average of 39.2 years. All diverticula were acquired, not congenital. Eight patients presented with acute appendicitis and diverticulitis, one patient presented with a normal appendix and acute diverticulitis, and one patient presented with periappendicitis with a noninflammatory diverticulum. Three patients also presented with mucoceles, one patient with a hyperplastic polyp, and two patients had a severe case of inflammation with epithelial regenerative atypia and mild dysplasia. The number of diverticula for each patient ranged from one to six. Multiple diverticula were present in 80% of the patients. In 90% of the patients, the diverticula were located in the distal portion of the appendix. Perforation was noted in seven (70%) patients. Conclusion The diverticula could have been preoperatively diagnosed with careful differentiation of the clinical presentations. High-resolution ultrasound or CT scans may facilitate diagnosis. The recommended treatment for asymptomatic appendiceal diverticulosis is prophylactic appendectomy because of the high perforation rate and a significant association with neoplasia. Once a surgical specimen is obtained, we advise conducting a thorough pathologic examination and securing additional sections to identify a greater number of diverticula, perforations, and associated neoplasms.

Background & aims Gastric cancer has familial clustering in incidence, and the familial relatives of gastric cancer sufferers are prone to have spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM) after H. pylori infection. This study tested whether serum pepsinogen I/II and trefoil factor family (TFF) proteins can predict SPEM or IM in the H. pylori-infected relatives of patients with gastric cancer. Methods We prospectively enrolled 119 H. pylori-infected relatives of gastric cancer patients of noncardiac gastric cancer patients, who then received panendoscopy to obtain gastric biopsy to define the presence of corpus gastritis index (CGI), SPEM, and IM. The advanced SPEM in histology was defined by TFF2 immunohistochemistry. Each patient also had checkups of serum TFF2, TFF3, and pepsinogen I/II by enzyme-linked immunosorbent assay (ELISA). Results The 119 H. pylori-infected relatives included 61 with SPEM, and 34 with IM. The presence of either IM or SPEM was not related to the serum TFF2, TFF3, and pepsinogen I/II levels (p > .05). Serum TFF2 levels were higher in relatives with CGI who also had advanced SPEM (p = .032). For relatives without CGI, the elevated serum TFF2 levels correlated with higher H. pylori density and more severe gastritis in antrum (p = .001). Conclusion The serum TFF2 level cannot predict SPEM or IM in H. pylori-infected relatives of patients with gastric cancer. For H. pylori-infected relatives with CGI, serum TFF2 levels may predict the advanced severity of SPEM. Elevated serum TFF2 levels may indicate severe H. pylori-related inflammation, at risk of development or progression of SPEM in relatives without CGI.

Background and Aim Intestinal metaplasia (IM) has overexpressions of COX-2. Short-term 8-week celecoxib, a selective COX-2 inhibitor, exerts a preliminary hint to improve regression in part for persistent IM after Helicobacter pylori eradication. This study further validated whether or not a prolonged duration of celecoxib of up to 1 year can be safe and effective. Methods One hundred and forty patients, with persistent IM after H. pylori eradication for 1 year, were included with half of them receiving celecoxib 200 mg/day for 12 months and the other half serving as controls. Each patient received serial checkups of blood creatinine levels every 4 months. After the 1-year follow-up, panendoscopy was repeated to assess the IM regression. The serial gastric specimens, taken before and after celecoxib therapy, were immunochemically stained for COX-2. Results The intention-to-treat (ITT) and per-protocol (PP) analyses to the rates of IM regression were higher in the celecoxib group than in the controls (ITT: 44.3% [31/70] vs 14.3% [10/70], p

Backgrounds: The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. Materials and Methods: Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) >1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. Results: All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p

The most critical factor for fracture union is the blood supply to the fracture site, which is usually impaired in patients with diabetes. Recently, mesenchymal stem cells-derived conditioned medium (MSC-CM) has shown significantly higher levels of angiogenic factors, such as VEGF and IL-6. We demonstrate in this report that MSC-CM delivered in gelatin sponges stimulates angiogenesis and promotes fracture healing in a diabetic rat model. Subcutaneous implantation of gelatin sponges soaked in MSC-CM demonstrated better tissue ingrowth and higher capillary densities at 2 and 3 weeks than gelatin sponges in minimal essential medium (MEM) or 293 cell-derived conditioned medium (293-CM). Implantation of fibular defects with gelatin sponges soaked in MSC-CM enhanced bone ingrowth and fracture healing rates compared to 293-CM and MEM groups at 8 weeks. Micro-computed tomography analysis further indicated a higher new bone volume in the MSC-CM group compared to the other diabetic groups. Histological analysis with CD31 immunostaining also revealed that MSC-CM increased endothelial cell counts compared to the other groups. Together, these results indicated that gelatin sponges used to deliver MSC-CM promote angiogenesis and fracture healing in a diabetic model and may be an alternative strategy for treating fracture non-union in patients with diabetes. Copyright © 2011 John Wiley & Sons, Ltd.

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

We tested whether cagL amino acid sequence polymorphisms of Helicobacter pylon correlated to clinico-histological outcomes and gastric alpha 5 beta 1 integrin expressions. One hundred forty five patients with H. pylori infection and 47 noninfected controls were enrolled to check gastric integrin alpha 5 beta 1 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%Cl: 1.8-11.9). H. pylon-infected patients had higher integrin alpha 5 beta 1 than noninfected patients (P < 0.05). Furthermore, cagL-Y58E59 H. pylori infection predisposed an upward shift in integrin alpha 5 beta 1 (P = 0.007) in the corpus, leading to more severe corpus chronic inflammation (P < 0.05). H. pylon CagL amino acid polymorphisms like Y58E59 correlate with a higher risk of GCA, and may regulate a corpus shift of gastric integrin alpha 5 beta 1 to lead to severe corpus gastritis during gastric carcinogenesis. (C) 2011 Wiley-Liss, Inc.

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.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.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 (P0.05). For gastric cancer patients, concomitant elevated MMP-3 (14 ng/ml) and MMP-7 (4.5 ng/ml) independently correlated with lymph node invasion (P0.05) and could be predictive to have shorter 2- or 5-year survivals (log rank test, P = 0.006).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.

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

H. pylori Eradication Prevents the Progression of Gastric Intestinal Metaplasia in Reflux Esophagitis Patients Using Long-Term Esomeprazole

Mixed infections with Helicobacter pylori facilitate interstrain gene transfer and the maintenance of genetic diversity for adaptation to the gastric environment, but whether mixed infections with histological significance and tissue tropism occur in the human stomach is still unclear. Helicobacter pylori was isolated from the antrum and the corpus of 30 dyspeptic patients. Four to eight colonies were randomly collected from each site. The genetic diversity of each isolate was evaluated by comparing random amplified polymorphic DNA banding patterns. The prevalence of mixed infections was 23.3% (7/30), and different dominant strains were isolated from the antrum and the corpus specimens. In the 23 patients infected with a single strain, the acute inflammation (Al) score, chronic inflammation (Cl) score, atrophy (AT) score and lymphoid follicle (LF) score of the antrum were usually higher than those of the corpus (p 0.05). Moreover, the patients with mixed infections had marginally higher CI and HPD scores than those with single-strain infection (p 0.062 and p 0.095, respectively) in the corpus and had a significantly higher rate of appearance of intestinal metaplasia (IM) in the antrum (p 0.005). These data show that H. pylori tissue tropism was found in the human stomach, and suggest that mixed infections could change the histological features in the antrum and in the corpus, and that they could be associated with the appearance of IM in the antrum.

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

A 50-year-old Taiwanese woman had a history of massive hemoptysis occurring every 6 months for the past 4 years. After each bout of hemoptysis, chest roentgenography would show diffuse alveolar infiltration of bilateral lungs, which would usually resolve within 7 days. Transbronchial biopsy revealed diffuse alveolar hemorrhage and hemosiderin-laden macrophage infiltration. Idiopathic pulmonary hemosiderosis was diagnosed by excluding other glomerular, cardiac and immunological disorders. An initial dose of 20 mg prednisolone daily was tapered to 10 mg daily 1 month later. The patient is currently undergoing steroid therapy, and there have been no further episodes of hemoptysis.

BACKGROUND AND STUDY AIM We investigated whether dental disease might be associated with a higher recurrence of Helicobacter pylori infection after successful eradication by triple therapy. PATIENTS AND METHODS Consecutive patients with successful H. pylori eradication, defined by negative results for both histology and (13)C-urea breath test (UBT) performed 6 weeks after triple therapy, were enrolled in the study. Each patient was scheduled for serial UBT and dental assessments at the end of the first, second, and third years. Patients were categorized into a "dental disease" group or "no dental disease" group at the first-year follow-up. Patients in the dental disease group whose dental disease had been cured during the second- and third-year follow-up periods, were transferred to a "dental treatment" group. RESULTS The first-year H. pylori recurrence rate was higher in the 159 patients with dental disease than in those 200 patients without dental disease (13.2 % vs. 3.5 %, P < 0.001; relative risk [95 %CI], 4.2 [1.7 - 10.1]). At both the second-year and the third-year follow-up, the annual H. pylori recurrence rates were higher in the dental disease group than in the no dental disease group or dental treatment group (second year, 18.4 % vs. 2.8 % or vs. 5.7 %, P < 0.001; third year, 20 % vs. 3.8 % or vs. 6.3 %, P < 0.001). CONCLUSION The presence of dental disease could predispose to recurrent H. pylori infection after successful eradication. Dental surveillance and care after H. pylori eradication is a rational step for preventing recurrence of H. pylori, especially in those with dental diseases.

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

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 13C-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 13C-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 13C-urea breath test ≤ 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 Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. Materials and Methods The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. Results H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. Conclusions H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.

Patients with squamous cell carcinomas (SCC) of upper aerodigestive tract, either over head and neck (HNSCC) or esophagus (ESCC), frequently developed synchronous multiple cancers, leading to worse prognosis. This study validated whether suppression of host cancer immunosurveillance mediated by regulatory T cells (Treg) may predispose to the development of synchronous cancers.Tumor tissues of 200 patients (100 ESCC only, 50 HNSCC only, and 50 synchronous SCCs) were quantitatively accessed for the tumor infiltrating Treg by immunohistochemistry. The density of Treg was also correlated to the level of Treg-associated inhibitory cytokines (IL-10, IL-35 and TGF-β1), and chemokine (CCL22).The density of tumor infiltrating Treg in the index tumor (i.e. the first malignancy diagnosed) of synchronous SCC group was higher than those of HNSCC or ESCC only (p0.05). Selecting the optimal cut-off value of Treg density as 34.6 cells/mm(2) by ROC curve, an increased Treg density of the index tumor can be an independent factor for developing synchronous SCCs (OR: 6.13; 95% CI: 2.84-13.26). The Treg density was positively correlated with serum IL-10 level and the degree of CCL22-positive cells infiltration in tumor. Furthermore, the serum inhibitory cytokine IL-10 level was higher in synchronous SCC than in non-synchronous ones (p0.001), that indicated the cellular immunosuppression in patients with synchronous cancers.A more severe defect in cellular immunity may predispose to multifocal tumor. The Treg cell number in SCC may serve as a novel predictive biomarker for the risk of synchronous cancer development to initiate a proper surveillance program.

Summary Background and Aim To test whether the chronic users of celecoxib, a selective cyclo-oxygenase-2 inhibitor, had less Helicobacter pylori-related intestinal metaplasia or if such users’ intestinal metaplasia could be prone to disappear after H. pylori eradication. Methods The study enrolled 150 chronic celecoxib users and 216 non-users who underwent pan-endoscopy to detect H. pylori infection and its related intestinal metaplasia. One hundred and three H. pylori-infected patients with intestinal metaplasia (43 chronic celecoxib users and 60 non-users) received anti-H. pylori therapy and completed the 12-month follow-up to survey the regression of intestinal metaplasia by mean intestinal metaplasia score. Results There were no differences in the prevalence of H. pylori-related intestinal metaplasia between the chronic celecoxib users and controls (P > 0.05). On the 12th month of follow-up, chronic celecoxib users had a lower mean intestinal metaplasia score (1.2 vs. 1.8, P

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.

Background. We tested whether Helicobacter pylori-infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori-infected children were predisposed to iron deficiency or growth retardation. Materials and methods. A total of 163 children from 106 dyspeptic mothers (58 with and 48 without H. pylori infection) were enrolled to evaluate body weight, height, hemoglobin, serum ferritin, and H. pylori infection using the 13C-urea breath test. A questionnaire was used to evaluate demographic factors of each child. Results. The rate of H. pylori infection in children with H. pylori-infected dyspeptic mothers was higher than that of children with noninfected mothers (20.5% vs. 5.3%; p

This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection.A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-alpha promoter SNP over the locus on -1031(T/C), -863(C/A), -857(C/T), -806(C/T), and -308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydney's system. Gastric TNF-alpha expressions were stained by immunohistochemistry.In H. pylori-infected patients, -1031C or -863A carriers of TNF-alpha promoter had more severe gastric neutrophil infiltration and TNF-alpha gastric staining than individuals with -1031TT or -863CC genotype, respectively (p0.05). The multivariate logistic regression verified both -1031C and -863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p0.05). As compared to -863CC and -1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32-4.59, por=0.00001) for the carriers with either -1031C or -863A allele, and even elevated to 6.06 (95% CI: 3.57-10.21, por=0.00001) for the individuals harboring both -863A and -1031C alleles. For patients with gastric ulcer, the 863CC genotype had a higher rate to have intestinal metaplasia than -863A carrier (por=0.005).TNF-alpha-1031 and -863 promoter SNP should be novel host factors to determine the gastric inflammation and risk of peptic ulceration upon H. pylori infection.

Primary pulmonary cryptococcosis is difficult to diagnose because the symptoms and radiologic findings are non-specific. Further, pulmonary cryptococcal infections are extremely rare in individuals with normal immunity. This case report describes a case of primary pulmonary cryptococcosis in an immunocompetent individual who presented with left upper lobe collapse due to endobronchial occlusion.

Purpose. We tested whether the serological response to Flavodoxin-A (FldA) protein and anti-Helicobacter pylori immunoblots correlated to the degree of mucosa-associated lymphoid tissue (MALT) in the stomach. Methods. Eighty H. pylori-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. pylori 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

Summary Aim : To identify optimal antibiotics for second-line quadruple therapy of Helicobacter pylori after failed 1-week triple therapy. Methods : One hundred patients were enrolled in this study after the failure of 1-week triple therapy. They were randomized to receive 1-week quadruple therapy consisting of amoxicillin, omeprazole and bismuth salts, plus either metronidazole or tetracycline. Before quadruple therapy, the H. pylori culture of each patient was tested for metronidazole resistance or clarithromycin resistance by E-test. Six weeks later, an endoscopy or 13C-urea breath test was used to define the success of H. pylori eradication. Results : The H. pylori eradication rates by intention-to-treat and per protocol analysis were higher in the tetracycline group than in the metronidazole group (intention-to-treat: 78% vs. 58%, P