Laryngopharyngeal reflux and Helicobacter pylori

Laryngopharyngeal reflux (LPR) occurs when gastric contents pass the upper esophageal sphincter, causing symptoms such as hoarseness, sore throat, coughing, excess throat mucus, and globus. The pattern of reflux is different in LPR and gastroesophageal reflux. LPR usually occurs during the daytime in the upright position whereas gastroesophageal reflux disease more often occurs in the supine position at night-time or during sleep. Ambulatory 24-h double pH-probe monitoring is the gold standard diagnostic tool for LPR. Acid suppression with proton pump inhibitor on a long-term basis is the mainstay of treatment. Helicobacter pylori (H. pylori) is found in many sites including laryngeal mucosa and interarytenoid region. In this paper, we aim to present the relationship between LPR and H. pylori and review the current literature.     

Helicobacter pylori infection and esophageal cancer risk:An updated meta-analysis

AIM:To clarify the association between Helicobacter pylori(H.pylori)infection and the risk of esophageal carcinoma through a meta-analysis of published data.METHODS:Studies which reported the association between H.pylori infection and esophageal cancer published up to June 2013 were included.The odds ratios(ORs)and corresponding 95%CIs of H.pyloriinfection on esophageal cancer with respect to health control groups were evaluated.Data were extracted independently by two investigators and discrepancies were resolved by discussion with a third investigator.The statistical software,STATA(version 12.0),was applied to investigate heterogeneity among individual studies and to summarize the studies.A meta-analysis was performed using a fixed-effect or random-effect method,depending on the absence or presence of significant heterogeneity.RESULTS:No significant association between H.pylori infection and esophageal squamous cell carcinoma(ESCC)risk was found in the pooled overall population(OR=0.97,95%CI:0.76-1.24).However,significant associations between H.pylori infection and ESCC risk were found in Eastern subjects(OR=0.66,95%CI:0.43-0.89).Similarly,cytotoxin-associated gene-A(CagA)positive strains of infection may decrease the risk of ESCC in Eastern subjects(OR=0.77,95%CI:0.65-0.92),however,these associations were not statistically significant in Western subjects(OR=1.26,95%CI:0.97-1.63).For esophageal adenocarcinoma(EAC)the summary OR for H.pylori infection and CagA positive strains of infection were 0.59(95%CI:0.51-0.68)and 0.56(95%CI:0.45-0.70),respectively.CONCLUSION:H.pylori infection is associated with a decreased risk of ESCC in Eastern populations and a decreased risk of EAC in the overall population.     

Simple animal model of Helicobacter pylori infection

Helicobacter pylori(H.pylori)has become accepted as a human pathogen for the development of gastritis and gastroduodenal ulcer.To develop a simple rat model of chronic H.pylori infection,male Sprague-Dawley rats were pretreated with streptomycin suspended in tap water(5 mg/mL)for 3 d.The rats were inoculated by gavage at 1 mL/rat with H.pylori suspension(5×108-5×1010 CFU/mL)twice daily at an interval of 4 h for three consecutive days.Two weeks after inoculation,rats were sacrificed and the stomachs were removed.Antral biopsies were performed for urease test and the stomachs were taken for histopathology.Successful H.pylori inoculation was defined as a positive urease test and histopathology.We reported a 69.8%-83.0%success rate for H.pylori infection using the urease test,and hematoxylin and eosin staining confirmed the results.Histopathological analysis detected bacteria along the mucous lining of the surface epithelium and crypt lumen and demonstrated mild to moderate gastric inflammation in successfully inoculated rats.We developed a simple rat model of chronic H.pylori infection for research into gastric microcirculatory changes and therapy with plant products.     

Factors that mediate colonization of the human stomach by Helicobacter pylori

Helicobacter pylori(H.pylori)colonizes the stomach of humans and causes chronic infection.The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells.The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease.Colonization of gastric mucus is likely to be key to the establishment of chronic infection.How H.pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review.We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals.H.pylori infection of the gastric mucosa has become a paradigm for chronic infection.Understanding of why H.pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.     

Diagnosing Helicobacter pylori infection in vivo by novel endoscopic techniques

Infection with Helicobacter pylori (H. pylori) is a worldwide problem. Endoscopic observation of H. pylori infection in vivo would be helpful to obtain an immediate diagnosis. The aim of this review is to describe recent advances in endoscopic technology and to review the available literature pertaining to its clinical application in H. pylori infection. Endoscopic visualization of H. pylori infection is not always feasible using conventional endoscopy. Thus, advanced endoscopic techniques have been developed with the aim of providing a precise and ‘‘real-time’’ endoscopic diagnosis. Recently, new endoscopic techniques such as magnifying endoscopy, narrow band imaging, I-Scan, endocytoscopy and endomicroscopy help focus examination of the stomach to diagnose disease in a time-efficient manner, and the analysis of mucosal surface details is beginning to resemble histologic examination. The new detailed images have enabled endoscopists to observe microscopic structures, such as gastric pit patterns, microvessels and cell morphology. Accordingly, endoscopic prediction of H. pylori infection is possible by analysis of surface architecture of the mucosa, which influences the clinical management. These endoscopic techniques might lead us to easier diagnosis and treatment of H. pylori-related diseases.     

Helicobacter pylori and skin autoimmune diseases

Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori(H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins(HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Beh et’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review.     

Management of Helicobacter pylori infection after gastric surgery

The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori(H.pylori)in patients with previous gastric neoplasia who have undergone gastric surgery.However,the guidelines do not mention optimal timing,eradication regimens,diagnostic tools,and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H.pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy.The purpose of this review is to provide an update which may help physicians to properly manage H.pylori infection in patients who have undergone gastric surgery.This review focuses on(1)the microenvironment change in the stomach after gastrectomy;(2)the phenomenon of spontaneous clearance of H.pylori after gastrectomy;(3)the effects of H.pylori on gastric atrophy and intestinal metaplasia after gastrectomy;(4)incidence and clinical features of ulcers developing after gastrectomy;(5)does eradication of H.pylori reduce the risk of gastric stump cancer in the residual stomach?(6)does eradication of H.pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach?and(7)optimal timing and regimens for H.pylori eradication,diagnostic tools and follow-up strategies for patients undergoing gastrectomy.     

Fluoroquinolone-based protocols for eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.     

Vaccine against Helicobacter pylori : Inevitable approach

Over three decades have passed since the discovery of Helicobacter pylori(H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.     

Antibiotics resistance rate of Helicobacter pylori in Bhutan

AIM:To survey the antibiotic resistance pattern of Helicobacter pylori(H.pylori)strains isolated from Bhutanese population.METHODS:We isolated 111 H.pylori strains from the gastric mucosa of H.pylori-infected patients in Bhutan in 2010.The Epsilometer test was used to determine the minimum inhibitory concentrations(MICs)of amoxicillin(AMX),clarithromycin(CLR),metronidazole(MNZ),levofloxacin(LVX),ciprofloxacin(CIP),and tetracycline(TET).RESULTS:Nineteen of the isolated H.pylori strains were susceptible to all antibiotics tested.The isolated strains showed the highest rate of antibiotic resistance to MNZ(92/111,82.9%).Among the 92 MNZresistant strains,74 strains(80.4%)showed high-level resistance(MIC≥256 g/mL).Three strains were resistance to LVX(2.7%).These strains were also resistance to CIP.None of the strains showed resistance to CLR,AMX and TET.CONCLUSION:CLR-based triple therapy is a more effective treatment approach over MNZ-based triple therapy for H.pylori infection in Bhutan.     

Helicobacter pylori eradication for preventing gastric cancer

Helicobacter pylori(H.pylori)infection is a major riskfactor for gastric cancer(GC)development,which isone of the most challenging malignant diseases worldwide with limited treatments.In the multistep pathogenesis of GC,H.pylori infection slowly induces chronicactive gastritis,which progresses through the premalignant stages of atrophic gastritis,intestinal metaplasia,and dysplasia,and then finally to GC.Although eradication of H.pylori is a reasonable approach for the prevention of GC,there have been some contradictory reports,with only some long-term follow-up data showingefficacy of this approach.The inconsistencies are likely due to the insufficient number of participants,relatively short follow-up periods,poor quality of study designs,and the degree and extent of preneoplastic changes atthe time of H.pylori eradication.This review analyzesrecent high-quality studies to resolve the discrepancies regarding the eradication of H.pylori for GC prevention.The relationship between H.pylori eradication and GC/precancerous lesions/metachronous GC is examined,and the cost-effectiveness of this strategy in the prevention of GC is assessed.Although it is assumed that eradication of H.pylori has the potential to prevent GC,the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined.As a result,additional well-designed trials with longer followup periods are needed to clarify this issue.     

The gastric microbial community,Helicobacter pylori colonization,and disease

Long thought to be a sterile habitat, the stomach contains a diverse and unique community of bacteria. One particular inhabitant, Helicobacter pylori, colonizes half of the world’s human population and establishes a decades-long infection that can be asymptomatic, pathogenic, or even beneficial for the host. Many host and bacterial factors are known to influence an individual’s risk of gastric disease, but another potentially important determinant has recently come to light: the host microbiota. Although it is unclear to what extent H. pylori infection perturbs the established gastric microbial community, and H. pylori colonization seems generally resistant to disturbances in the host microbiota, it can modulate H. pylori pathogenicity. Interactions between H. pylori and bacteria at non-gastric sites are likely indirect—via programming of the pro-inflammatory vs. regulatory T lymphocytes—which may have a significant impact on human health.     

Helicobacter pylori infection following partial gastrectomy for gastric cancer

Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer.The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer.Helicobacter pylori(H.pylori)infection is also a well-known characteristic of gastric carcinogenesis.H.pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis;however,the H.pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis.For instance,H.pylori infection of the gastric stump produced controversial results in several recent studies.The prevalence of H.pylori infection in the gastric stump has varied among recent reports.Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ.Bilerefluxate also has a significant influence on the colonization of the stomach stump,with several studies reporting mixed results as well.In contrast,the elimination of H.pylori from the gastric stump has shown a dramatic impact on eradication rate.H.pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers.To overcome the current discrepancies in the literature regarding the role of H.pylori in the gastric stump,further research is required.     

Helicobacter pylori infection in older people

Since the discovery of Helicobacter pylori(H.pylori)infection as the major cause of gastroduodenal disorders three decades ago,H.pylori has been the focus of active research and debate in the scientific community.Its linkage to several diseases,such as peptic ulcer disease,gastritis and gastric malignancy is incontestable.In particular,it has been noticed that,as the aged population is increasing worldwide,older people are at increased risk of developing several gastroduodenal diseases and related complications.At the same time,gastric cancer is definitely more frequent in elderly than in adult and young people.In addition,it has been showed that peptic ulcer and related complications occur much more commonly in aged individuals than in young people,resulting in a significantly higher mortality.Although this infection plays a crucial role in gastrointestinal disorders affecting all age groups and in particular older people,only a few studies have been published regarding the latter.This article presents an overview of the epidemiology,diagnosis,clinical manifestations and therapy of H.pylori infection in elderly people.     

Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

Background/Aims

This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori.

Methods

We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d., levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week.

Results

In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively.

Conclusions

A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori.     

Helicobacter pylori colonization of the oral cavity:A milestone discovery

Over the past several years, the severity of Helicobacter pylori(H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due tooral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization.     

Helicobacter pylori:Management in 2013

Helicobacter pylori(H.pylori)is a prevalent,worldwide,chronic infection.Choice of treatment can be modified according to antibiotic-resistance rates of H.pylori.The ideal therapeutic regimen for H.pylori infection should achieve an eradication rate of≥80%.In some countries,triple therapy with a proton-pump inhibitor(PPI),clarithromycin,and amoxicillin or metronidazole is still the best option.Bismuth-containing quadruple therapy consisting of bismuth salts,tetracycline,metronidazole and PPI,may be the preferred option in countries with clarithromycin resistance>20%.Sequential therapy including a PPI and amoxicillin given for the first 5 d,followed by triple therapy including a PPI,clarithromycin,and nitroimidazole antimicrobial(all twice daily)for the remaining 5 d,can be another option for the first-line treatment of H.pylori.Recent data suggest that treatment with PPI,levofloxacin,and amoxicillin for 10 d is a good choice for second-line therapy.Concomitant therapy consisting of PPI,amoxicillin,clarithromycin and metronidazole is another option for second-line treatment.If second-line treatment also fails,it is recommended to culture H.pylori from biopsy specimens and perform antimicrobial susceptibility testing.Rescue treatment should be based on antimicrobial susceptibility.     

Biofilm and Helicobacter pylori:From environment to human host

Helicobacter pylori(H.pylori)is a Gram negative pathogen that selectively colonizes the human gastric epithelium.Over 50%of the world population is infected with H.pylori reaching up to 90%of infected individuals in developing countries.Nonetheless the increased impact upon public health care,its reservoir and the transmission pathway of the species has not been clearly established yet.Molecular studies allowed the detection of H.pylori in various aquatic environments,even forming biofilm in tap water distribution systems in several countries,suggesting a role of water as a possible reservoir of the pathogen.The persistence of human infection with H.pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm,demonstrated both in vivo and in vitro experiments.Thus,during the last years,experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents.However,only two anti-H.pylori biofilm disrupting agents have been successfully used:Curcumin-a natural dye-and N-acetyl cysteine-a mucolytic agent used in respiratory diseases.The main goal of this review was to discuss the evidences available in the literature supporting the ability of H.pylori to form biofilm upon various surfaces in aquatic environments,both in vivo and in vitro.The results published and our own observations suggest that the ability of H.pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans,mainly through natural water sources and water distribution systems.