Helicobacter pylori infection in gastric remnant cancer after gastrectomy

Patients who have undergone distal gastrectomy for peptic ulcer are at higher risk of developing gastric remnant cancer, and chronic bile reflux is believed to increase the risk of cancer in remnant stomach. In remnant stomach, carcinogenesis may be prevented by selecting the anastomosis method with a few reflux of intestinal juice including a bile acid. How Helicobacter pylori(H. pylori) infection participate in stomal gastritis and gastric remnant cancer, same as early gastric cancer in the intact stomach, is attended. H. pylori positive rate of remnant stomach is different by examination method and a report, but its rate is decreased every year after gastrectomy and in particular low in Billroth-II(B-II) anastomosis. B-II anastomosis is followed by a significantly lower rate than B-1. This may reflect the role of bile reflux because bile reflux interferes with colonization by H. pylori. Gastric cancer excision usual increase complicates gastric remnant stomach and H. pylori infection, but while H. pylori infection lasts after gastrectomy for gastric cancer, cell proliferation increase in remnant stomach. In remnant stomach after gastrectomy for gastric cancer, while H. pylori infection continues, H. pylori infection may cause remnant gastritis and a second cancer of remnant stomach. H. pylori infection and bile reflux seem to have a synergistic effect on cell proliferation in remnant stomach and may explain the increased risk of gastric remnant cancer. The cancer-causing dominant role might changed from H. pylori infection predominance to bile reflux every year after gastrectomy. Furthermore, a prophylactic effect to carcinogenesis by H. pylori eradication therapy is expected. Eradication of H. pylori after gastrectomy for gastric cancer has been recommended.     

Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy.

Helicobacter pylori causes gastritis and peptic ulcers and is linked to gastric cancer. Domestic cats from a commercial source were found to be naturally infected with H. pylori, and studies were undertaken to eradicate H. pylori from infected cats by using triple antimicrobial therapy. Eight cats infected with H. pylori were used in the study. Six cats received a 21-day course of oral amoxicillin, metronidazole, and omeprazole, and two cats served as controls. Two weeks and 4 weeks posttreatment (p.t.), all six treated cats were negative at several sites (saliva, gastric juice, and gastric mucosa) for H. pylori by culture. However, as determined by PCR with primers specific for the 26-kDa product, the majority of cats at 2 and 4 weeks p.t. had gastric fluid samples which were positive for H. pylori and three of three cats at 2 weeks p.t. had dental plaque which was positive for H. pylori. At 6 weeks p.t., all six cats had H. pylori-negative cultures for samples from several gastric sites taken at necropsy, and only one cat had H. pylori cultured from gastric juice. PCR analysis revealed that five of six cats had H. pylori DNA amplification products from plaque, saliva, and/or gastric fluid samples. Negative bacterial cultures for cats for which there was demonstrable PCR amplification of H. pylori DNA may reflect the inability of in vitro culture techniques to isolate small numbers of H. pylori organisms, focal colonization at sites not cultured, or a failure of the antibiotics to successfully eradicate H. pylori from extragastric sites which allowed subsequent recolonization of the stomach after cessation of therapy. Alternatively, the treatment strategy may have induced in vivo viable but nonculturable coccoid forms of H. pylori. The H. pylori cat model should allow further studies to test these hypotheses as well as the efficacies of other combined therapeutic regimens. Also, because 100% of these cats were naturally infected with H.pylori, this model should prove useful in exploring mechanisms whereby human populations in underdeveloped countries, which have H. pylori infection rates approaching 100%, have a high rate of recurrence of H. pylori infection after use of prescribed antibiotic therapies that successfully eradicate H. pylori in individuals in developed countries.     

Oral colonization of Helicobacter pylori: risk factors and response to eradication therapy

BACKGROUND: Dental plaque is considered by some to be a secondary reservoir for Helicobacter pylori and thus responsible for gastric reinfection. The aim of this study was to investigate whether testing dental plaque using a rapid urease test (CLOtest) can be used to determine gastric H. pylori status. METHODS: We investigated dental plaque colonization by H. pylori and its correlation with gastric infection in 75 dyspeptic patients. CLOtest was used to determine H. pylori positivity. RESULTS: Tests for H. pylori were positive in dental plaque samples from 68 patients and in stomach samples from 65 patients. The sensitivity of using CLOtest in dental plaque to determine gastric H. pylori status was 89.7%, with a diagnostic accuracy of 86.7%. Gastric eradication was achieved in 83% of patients, but efforts to eradicate dental plaque colonization were unsuccessful in all patients. CONCLUSION: Using CLOtest to detect H. pylori in dental plaque is a reliable first-line diagnostic approach for gastric H. pylori infection. Dental plaque might be a sanctuary for H. pylori, leading to gastric recurrence.     

Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37

The human gastric pathogen Helicobacter pylori steals host cholesterol, modifies it by glycosylation, and incorporates the glycosylated cholesterol onto its surface via a cholesterol glucosyltransferase, encoded by cgt. The impact of cholesterol on H. pylori antimicrobial resistance is unknown. H. pylori strain 26695 was cultured in Ham's F12 chemically defined medium in the presence or absence of cholesterol. The two cultures were subjected to overnight incubations with serial 2-fold dilutions of 12 antibiotics, six antifungals, and seven antimicrobial peptides (including LL-37 cathelicidin and human alpha and beta defensins). Of 25 agents tested, cholesterol-grown H. pylori cells were substantially more resistant (over 100-fold) to nine agents than were H. pylori cells grown without cholesterol. These nine agents included eight antibiotics and LL-37. H. pylori was susceptible to the antifungal drug pimaricin regardless of cholesterol presence in the culture medium. A cgt mutant retained cholesterol-dependent resistance to most antimicrobials but displayed increased susceptibility to colistin, suggesting an involvement of lipid A. Mutation of lpxE, encoding lipid A1-phosphatase, led to loss of cholesterol-dependent resistance to polymyxin B and colistin but not other antimicrobials tested. The cgt mutant was severely attenuated in gerbils, indicating that glycosylation is essential in vivo. These findings suggest that cholesterol plays a vital role in virulence and contributes to the intrinsic antibiotic resistance of H. pylori.     

Indication of H. pylori eradication therapy

In the guideline, for H. pylori the Japanese Society of Helicobacter published diagnosis and treatment in July 2000. Only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. In addition, Japanese social security foundation approves only peptic ulcers for indication of H. pylori eradication treatment. However, eradication therapy for atrophic gastritis should be considered in aspect of decreasing gastric cancer risk. Since accumulated epidemiological, experimental and clinical data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer should be included for a target eradication therapy. Indication of the treatment should be expanded to histological gastritis caused by H. pylori in our country, where prevalence of gastric cancer is very high.     

Detection of Helicobacter pylori virulence-associated genes

Helicobacter pylori is an important human pathogen and persistent colonization of the human gastric mucosa can cause severe gastrointestinal diseases. The bacterium should not be considered as a uniform organism, but as a population of closely related and yet genetically diverse bacteria. Several genes of H. pylori (such as vacA and cagA) have been identified as being virulence-associated and may have important clinical and epidemiological implications. Assessment of virulence-associated genes of H. pylori should be included in clinical and epidemiological studies as well as therapeutic trials, in order to stratify between patient groups, harboring H. pylori strains with particular virulence genotypes. Molecular determination of antibiotic resistance will be especially useful for treatment studies. Together with our increasing knowledge about the human genome, typing of H. pylori will facilitate the management of gastroenterological pathologies.     

Helicobacter pylori: aggressor or innocent bystander?

Helicobacter pylori seeks gastric mucosa, whether found in the stomach, duodenum, or Barrett's esophagus. Definitive diagnosis can be secured by appropriate stains of mucosal biopsies and culture, but the rapid urease test, breath isotope studies, and serologic testing are also useful. The frequency of colonization increases with advancing age, but infection occurs earlier in underdeveloped countries. Although the reservoir is uncertain, water or food transmission seems likely. There is sufficient evidence to assign an etiologic role to the bacteria in the causation of type B antral gastritis. H. pylori is found in areas of gastric metaplasia within the duodenum and is associated with duodenitis. Although acute infection leads to hypochlorhydria, chronic colonization has little effect on acid secretion. Studies have thus far failed to establish a convincing relationship between H. pylori and nonulcer dyspepsia, although the bacteria may play a role in selected patients. H. pylori is found in association with most idiopathic gastric and duodenal ulcers, but it is unclear as to whether the bacteria plays a causative or permissive role. The organism has a predilection for intercellular spaces and the mucous layer, thus affording relative isolation from luminally active antibiotics. Monotherapy with bismuth preparations transiently eliminates the bacteria, but recolonization is rapid, probably due to regrowth of sequestered organisms. A combination of metronidazole, bismuth, and tetracycline (or amoxicillin) affords the best eradication rate, but the potential side effects of this program should be considered. The present therapy of duodenal ulcer disease is effective and without significant risk. Treatment of H. pylori should be reserved for those patients who relapse on adequate maintenance therapy. If a safe and effective antibiotic becomes available, more frequent testing and earlier treatment intervention may become more attractive. H. pylori is probably an "innocent bystander" for most patients, but the bacteria may sufficiently impair the defenses of the antral and duodenal mucosa to facilitate the development and relapse of ulcer disease in subsets of patients.     

幽门螺杆菌的根治对肝硬化患者血氨的影响

目的评价肝硬化患者Hp感染状况对血氨浓度的影响。方法对46例肝硬化伴高血氨患者的血液以及胃液中氨浓度进行分析,所有患者给予低蛋白饮食、卡那霉素、乳果糖以及丰富的支链氨基酸溶液治疗,其中24例患者仍有高血氨,根据Hp感染分布的状况,把24例患者分成三组：Hp在胃中弥漫性分布的患者为Ⅰ组,Hp在胃中局部分布的患者为Ⅱ组,Hp阴性的患者为Ⅲ组。24例患者均给予口服10mg雷贝拉唑,1000mg阿莫西林以及400mg克拉霉素或500mg甲硝唑2周进行Hp的根治。结果第Ⅰ组Hp根治后血液以及胃液中血氨浓度明显下降,Hp根治12周后血氨浓度明显降低（P〈0．05）,第Ⅱ组、Ⅲ组进行Hp根治后血氨浓度未见明显降低。结论胃中Hp弥漫性感染是导致肝硬化患者血氨升高的原因之一,针对Hp弥漫性分布的肝硬化患者,必须进行有效的Hp根治。     

Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation

Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer. However, structural evidence showing a quantitative relationship between the adherence of H. pylori and severity of gastric mucosal inflammation is lacking. We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H. pylori. Fifty-seven biopsy specimens from the gastric bodies of patients with H. pylori-induced gastritis were examined. The severity of gastritis and the adherence and structure of H. pylori were determined with the use of light and scanning electron microscopy. We also investigated the ability of H. pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H. pylori-associated gastritis. Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H. pylori to the epithelial surface were examined. The results indicated that H. pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli. Histologically, those gastric mucosa samples with H. pylori firmly attached showed severe gastritis. H. pylori bacilli of greater length induced higher levels of interleukin-8 secretion. The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H. pylori adhesion (r = -0.401, P <.01). We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H. pylori (r = 0.344, P <.05). A quantitative correlation was found between adherence of H. pylori and gastric inflammation. Both adherence and the induction of inflammation were found to be related to the structure of H. pylori.     

Indication of H. pylori eradication therapy--who should be treated?

With increased evidence of H. pylori infection being deeply related with various gastric diseases, its curative therapy will be approved by social security foundation soon also in Japan. Japanese Society of Helicobacter reported a guideline for H. pylori diagnosis and treatment in July 2000. In the guideline, only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. It is speculated that while benefit of eradication therapy for peptic ulcers and low grade MALT lymphomas has been supported by much clinical evidence, that for other diseases was judged not to be enough. Especially as to atrophic gastritis, eradication therapy might be considered in aspect of decreasing gastric cancer risk in Japan. Since accumulated epidemiological and experimental data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer could be included for a target eradication therapy. In present, indication of the therapy should be clinically and socially decided according to individual patient.     

幽门螺杆菌感染对胃粘膜细胞动力学的影响

应用流式细胞技术对Ｈｐ阳性和阴性患者胃粘膜细胞动力学进行对比研究，并以体外培养Ｈｐ所制备的Ｈｐ提取液灌喂大鼠，观察其对大鼠胃粘膜细胞周期的影响。结果表明，Ｈｐ阳性胃粘膜Ｓ期细胞和增殖指数均显著高于Ｈｐ阴性胃粘膜。Ｈｐ提取液可刺激大鼠胃粘膜细胞增殖指数和Ｓ期细胞显著增加。提示Ｈｐ可能通过刺激胃粘膜细胞增殖加速，更新加快，增加ＤＮＡ受损的机会，从而增加患胃癌的危险性。     

Virulence gene of H. pylori

H. pylori is a well-recognized pathogen that infects up to 50% of humans in the world. H. pylori lives for decades in the hostile environment of the human stomach. H. pylori is closely associated with histologic gastritis, gastric ulceration, duodenal ulceration, gastric cancer and MALT lymphoma. These various clinical outcomes are considered by 1) different virulence, 2) host response, 3) other environmental factors, and their interactions. Since the whole genome was sequenced in 1997, the virulence genes have been investigated in molecular genetic aspects. The cag pathogenicity island (cagPAI) is a complex of virulence genes, which code approximately 30 proteins. The cagPAI acquired by horizontal transfer and is coding for type 4 secretion machinery system. Via this system, many virulence gene products or other interactive proteins are transferred into the host cells.     

幽门螺杆菌感染的理想检测部位

以Warthin－Starry染色检测幽门螺杆菌（HP），HE染色观察胃炎程度，观察了90例HP阳性患者在胃底、胃体、角切迹、幽门前区大弯的分布情况和177例患者的胃糜烂部位与非糜烂部位的HP感染状况，发现：HP感染至全胃分布，各部位HP阳性率无明显差异（P＞0．05），但HP数量和胃炎程度有差异且二者有明显相关性（r=0．948），以角切迹HP数量最多、胃炎程度最重、局灶萎缩性胃炎和活动性胃炎的发生率亦最高；胃窦、胃体、胃底的HP数量、胃炎程度则依次降低。非糜烂部位的HP检出率为62．7％，糜烂部位的HP检出率为58．8％，二者无明显差异（P＞0．05），四型糜烂间HP检出率无显著性差异（P＞0．05）。结果提示：胃角切迹是检测HP感染、观察胃炎程度的理想部位，从糜烂部位取活检不一定能提高HP检出率。     

Laboratory tests for the evaluation of Helicobacter pylori infections.

Helicobacter pylori is a highly motile bacterium with multiple unipolar flagella, and it produces the urease enzyme. The flagella and urease are the virulence factors of H. pylori. H. pylori often establishes a chronic infection in the stomach that may lead to gastric and duodenal ulcers, gastric cancers, gastric lymphomas, and other gastrointestinal diseases. There are several different invasive and noninvasive clinical laboratory tests for H. pylori. Laboratory testing is not indicated in asymptomatic patients and should be considered only if treatment of H. pylori infection is planned. Invasive tests for H. pylori, such as tissue histology, culture, and rapid urease tests, are used if an endoscopy is performed on the patient. The noninvasive tests for H. pylori, such as enzyme antibody and urea breath tests, are recommended in patients whose symptoms do not warrant endoscopy. The urea breath test is very useful and is recommended to evaluate effectiveness in the eradication and treatment of H. pylori infections. Nucleic acid tests can complement other diagnostic procedures, and are useful in evaluating fixed biopsy tissue, environmental samples, gastric juices, oral secretions, and stool samples.     

Receptor-mediated targeting of lipobeads bearing acetohydroxamic acid for eradication of Helicobacter pylori.

In the present context, phosphatidyl ethanolamine (PE) liposomes anchored polyvinyl alcohol (PVA) xerogel beads (lipobeads) bearing acetohydroxamic acid (AHA) was developed as a receptor-mediated drug delivery system for use in blocking adhesion of Helicobacter pylori and thereby preventing the sequelae of chronic gastric infections. PVA beads containing AHA were prepared by emulsification followed by low temperature crystallization method. Surface acylation with fatty acid chain was accomplished by treating PVA bare beads with palmitoyl chloride. The completion of this reaction was characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) which confirmed the formation of an ester bond. Final formation of lipobeads was accomplished by combining acylated PVA beads with a PE liposome suspension. To confirm the specific binding propensity of lipobeads towards the PE specific surface receptors of H. pylori, we have performed in situ adherence assay and radiolabelling assay with human stomach cells and KATO-III cells, respectively. In both of these studies, pretreatment of H. pylori with lipobeads completely inhibited the adhesion of H. pylori to human stomach cells and KATO-III cells. These assays could serve as suitable in-vitro models for the study of binding efficacy of lipobeads with H. pylori surface receptors. In addition, the antimicrobial activity of the formulations was evaluated by growth inhibition (GI) studies with isolated H. pylori strain. The inhibitory efficacy of lipobeads was significantly higher compared to that of PVA bare beads. These results suggest that lipobeads could be a potential targeted drug delivery system in the treatment of H. pylori.     

Molecular markers in Helicobacter pylori-associated gastric carcinogenesis

Helicobacter pylori infection is a known risk factor of gastric carcino-genesis. This article presents early molecular alterations associated with H. pylori chronic gastritis and advances in the molecular characterization of preneoplastic intestinal metaplasia (IM) and premalignant gastric mucosal lesions. H. pylori infection induces changes in gene expression, genomic instability and accumulation of gene mutations in the stomach epithelium. Mutations, including LOH and microsatellite instability, and gene hypermethylation are seen not only in gastric cancer, but are already detectable in IM and gastric dysplasia/adenoma. Recent reports using microarray expression analysis identified several gastric epithelial genes that are regulated by H. pylori. Among the many genes showing altered epithelial expression in response to H. pylori, some might be useful as markers to assess gastric cancer risk. Profiles of mutagenesis and gene expression in IM and dysplasia/adenoma have been characterized and represent potential markers of preneoplastic and premalignant lesions during gastric carcinogenesis.     

Helicobacter pylori-related cytokines influence gastric acid secretion and gastric mucosal inflammation in gastroduodenal ulcers

Helicobacter pylori(H. pylori) is an important pathogenic factor for gastroduodenal ulcers and gastric cancer. The level of gastric acid output may influence the outcome of those diseases. With low acid output, H. pylori can spread to the corpus of the stomach, resulting in progression to atrophic gastritis. It may cause an increased risk of gastric cancer and ulcer. In contrast, with high output, H. pylori is confined in the gastric antrum, which develops antrum-predominant gastritis. This may contribute to an increased risk of duodenal ulcer. It is well known that inflammatory cytokines including interleukin (IL)-1 beta, IL-8 and tumor necrosis factor alpha modulate gastric acid secretion. Therefore, the host immune response by the cytokines may cause these disparate pathways in gastric acid secretion.     

中国幽门螺杆菌感染的现状

我国是幽门螺杆菌（HP）高感染地区，HP感染相关疾病负担（尤其是胃癌）较重，国内学术界应尽快统一认识，重视HP感染的危害，建立有效的胃癌一、二级预防体系；同时，随着近年来抗生素耐药率的不断上升，传统方案根除率逐年下降，临床医师应参照最新共识，规范HP感染的诊治，重视提高初次HP根除率。     

Exploring novel vaccines against Helicobacter pylori: protective and therapeutic immunization

Infection of human stomach by Helicobacter pylori, a gram negative spiral bacterium first isolated in 1983 from a patient with chronic active gastritis (1), causes nearly all duodenal ulcers and most gastric ulcers and is associated with an increased risk of gastric adenocarcinoma (2). Current therapies for gastric infections include combination triple or quadruple therapy of antimicrobial and/or antiulcer agents for eradication of H. pylori infection (3). Development of the resistant strains and ecological niche (habitant) of the bacteria may cause relapse after the termination of the therapy. However, if effective, the high cost, difficulty of patient compliance and risk of selection for resistant strains make these therapeutic regimens impractical on a large scale, though effective on the laboratory trial stages. Studies of the pathogenesis of H. pylori have led to the identification of bacterial antigens and adherin proteins as candidates for inclusion as novel vaccines against these diseases (4-7). Both prophylactic and therapeutic vaccination have been demonstrated in animal models of H. pylori infection (8-10).     

Helicobacter pylori induces beta3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x

Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (SabA), which binds the carbohydrate structure sialyl-Lewis x. Sialyl-Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-related gene expression profile of a human gastric carcinoma cell line following H. pylori infection. We observed that H. pylori significantly altered expression of 168 of the 1,031 human genes tested by microarray, and the extent of these alterations was associated with the pathogenicity of the H. pylori strain. A highly pathogenic strain altered expression of several genes involved in glycan biosynthesis, in particular that encoding beta3 GlcNAc T5 (beta3GnT5), a GlcNAc transferase essential for the biosynthesis of Lewis antigens. beta3GnT5 induction was specific to infection with highly pathogenic strains of H. pylori carrying a cluster of genes known as the cag pathogenicity island, and was dependent on CagA and CagE. Further, beta3GnT5 overexpression in human gastric carcinoma cell lines led to increased sialyl-Lewis x expression and H. pylori adhesion. This study identifies what we believe to be a novel mechanism by which H. pylori modulates the biosynthesis of the SabA ligand in gastric cells, thereby strengthening the epithelial attachment necessary to achieve successful colonization.