Forty years of Helicobacter pylori infection and changes in findings at esophagogastroduodenoscopy.

BACKGROUND: It is 40 years since the discovery of Helicobacter pylori infection. Over that time major changes have occurred in esophagogastroduodenoscopy (EGD) findings. The aim of this review is to describe these changes, and the important role H. pylori infection has played in their evolution. METHODS: References were identified through searches of PubMed using the search terms-endoscopy time trends, peptic ulcer disease, gastroesophageal reflux disease, upper gastrointestinal cancer, gastric polyps, H. pylori, eosinophilic gastrointestinal disorders, and celiac disease, from 1970 through December 2021. RESULTS: The prevalence of H. pylori infection has fallen and consequently, H. pylori-positive peptic ulcer disease has become rare. Gastroesophageal reflux disease is now the commonest disorder diagnosed at EGD, and Barrett's esophagus has increased in parallel. Cancer of the distal stomach has fallen while esophageal adenocarcinoma and reflux-related cardia cancer have risen. Gastric polyps have changed from hyperplastic and adenomas to sporadic fundic gland polyps. Antimicrobial resistance has made H. pylori infection more difficult to eradicate. Eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, have emerged as important new allergic disorders. Celiac disease has changed and increased. CONCLUSIONS: EGD findings appear to have changed from features suggesting a H. pylori-positive "phenotype" 40 years ago to a H. pylori-negative "phenotype" today. These changes have major implications for the management of gastrointestinal disorders.

A randomized-controlled study to compare the efficacy of sequential therapy with standard triple therapy for Helicobacter pylori eradication in an Irish population.

INTRODUCTION: Eradication rates for the standard first-line triple therapy for Helicobacter pylori infection have decreased in recent years. Sequential therapy has been suggested as an alternative. The efficacy of sequential therapy has not been assessed to date in an Irish population. OBJECTIVE: The aim of this study was to compare the efficacy of standard triple therapy with sequential therapy for H. pylori eradication. PATIENTS AND METHODS: A prospective randomized-controlled study was carried out. Treatment-naive H. pylori-infected patients were randomized to receive either standard triple therapy or sequential therapy. RESULTS: In all, 87 eligible patients were recruited into the study, one of whom dropped out. Fifty-one per cent (N=44) patients received standard triple therapy and 49% (N=42) patients received sequential therapy. The eradication efficacy by intention-to-treat analysis was 56.8% [N=25/44; 95% confidence interval (CI) 42.2-71.4%] for standard triple therapy and 69% (N=29/42; 95% CI 55.0-83.0%) for sequential therapy. The eradication rates by per-protocol analysis for standard triple therapy and sequential therapy were 61% (N=25/41; 95% CI 46.1-76.0%) and 69% (N=29/42; 95% CI 55.0-83.0%), respectively. The differences in eradication rates for each treatment by either intention-to-treat or per-protocol analysis were not statistically significant (P=0.24 and 0.44, respectively). In addition, incidence in adverse events was not significantly different between the study groups. The most common adverse event reported was mild nausea at 15% (95% CI 7.5-22.6%). CONCLUSION: Sequential therapy had a nonstatistically significant advantage over standard triple therapy in our patient cohort. However, eradication rates for both standard triple therapy and sequential therapy were suboptimal. Further studies are required to identify potential alternatives to standard first-line triple therapy.

Practical treatment of Helicobacter pylori: a balanced view in changing times.

Eradication rates of first-line triple therapy for Helicobacter pylori infection have fallen in the recent years. The main reasons for treatment failure are poor compliance due to complicated treatment regimens and the emergence of antibiotic-resistant strains of H. pylori. Treatment failure is a cause for concern with regard to the complications of H. pylori infection, which include gastric and peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. This review describes considerations for optimizing standard first-line triple therapy, as well as alternatives to the standard first-line treatment, such as bismuth quadruple therapy, sequential therapy, concomitant therapy and hybrid therapy. Studies using levofloxacin-based and rifabutin-based regimens for the treatment of multiresistant infections have also been reviewed. The current most up-to-date systematic reviews and meta-analyses comparing the efficacy of these treatments have been discussed, in light of the recent antimicrobial susceptibility testing data, regional antibiotic resistance rates and the Maastricht IV guidelines on the management of H. pylori infection.

Isolated active ileitis: is it a mild subtype of Crohn's disease?

BACKGROUND: Ileal intubation is being increasingly performed at colonoscopy and has in turn lead to an increasingly recognized subgroup of patients-those with mild terminal ileal inflammation, an entity that we have coined isolated active ileitis (IAI). The aims of this study were to define the natural history of IAI and determine if IAI shares a similar genetic and serologic profile with Crohn's disease (CD). METHODS: Patients with IAI were identified from our institution's histopathology and endoscopy databases. Cases attended for repeat colonoscopy and blood were analyzed for the expression of antineutrophil cytoplasmic antibody, anti-OmpC, anti-Saccharomyces cerevisiae antigen (ASCA) IgA, ASCA IgG, and anti-CBir antibodies and NOD2 genotyping. Age and sex-matched healthy controls, CD, and UC cases were also recruited. RESULTS: Sixty-three patients with IAI were recruited. There was no significant difference in the prevalence of antibodies between IAI cases and healthy controls for antineutrophil cytoplasmic antibody, OmpC, ASCA IgA, or ASCA IgG. The presence of all 5 antibodies was significantly higher in the CD group than the IAI group, P < 0.05. There were 28.6% of CD cases that carried one or more NOD2 variants, compared to 26.2% of the IAI cohort and 6.1% of healthy controls. Forty-three cases underwent follow-up ileocolonoscopy. Six of 43 cases (14%) had definite CD. CONCLUSIONS: A majority of IAI cases developed persistent symptoms and terminal ileal abnormalities; however, only 14% developed classical, histological, or radiological features of CD. Although patients with IAI have a low level of seropositivity, similar to healthy controls, they do share an excess of NOD2 mutations with CD cases.

Helicobacter pylori and nonmalignant diseases.

Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.

Eosinophilic oesophagitis: an Irish experience.

INTRODUCTION: Eosinophilic oesophagitis is a recently recognized oesophageal disorder characterized by a combination of clinical and endoscopic features as well as the histological finding on oesophageal biopsy of greater than 15 eosinophils per high powered field. Recent reports suggest eosinophilic oesophagitis is increasing in incidence and this increase cannot be fully explained by increased recognition of the disorder. The aim of this retrospective study was to assess the incidence of eosinophilic oesophagitis within the catchment area of a tertiary referral hospital in southwest Dublin, Ireland. METHODS: The histopathology database at the Adelaide and Meath Hospital was used to identify all oesophageal biopsies obtained between January 2000 and July 2008 reported to show evidence of oesophagitis. Biopsy samples with greater than 15 eosinophils per high powered field in at least two fields were highlighted as possible eosinophilic oesophagitis. The oesophageal biopsies of patients identified in this way were reviewed by a histopathologist with a special expertise in gastroenterology for features suggestive of eosinophilic oesophagitis. RESULTS: Twenty-five thousand three hundred and sixty-five upper gastrointestinal endoscopies were performed between January 2000 and July 2008. A total of 11 072 sets of oesophageal biopsies were taken and 1364 (12.3%) of these revealed evidence of oesophagitis. Only 13 (0.1%) patients had oesophageal biopsies showing greater than 15 eosinophils per high powered field. The median age of this patient group was 23 years (interquartile range 10.5-50.5 years), with 46% of patients under 18 years at the time of diagnosis. The male to female ratio was 5.5 : 1 compared with 1.1 : 1 in the oesophagitis group as a whole, (P=0.002). There was no significant association between endoscopic findings or presenting complaints and the average number of eosinophils per high powered field. The average number of biopsies taken in patients with endoscopic findings suggestive of eosinophilic oesophagitis was 3.75 compared with 1 in patients without those features, (P=0.01). CONCLUSION: Our findings suggest that eosinophilic oesophagitis is a rare disorder predominantly affecting young men.

Safety of infliximab in 10 years of clinical practice.

UNLABELLED: Assessment of the long-term safety of anti-tumour necrosis factor therapies is vital for the safe treatment of inflammatory bowel disease, a disease affecting a young cohort of patients. AIMS: The aim of this retrospective study was to assess the safety and long-term outcome of infliximab use in clinical practice in our institution on an intention to treat basis over the 10-year period from December 1998 to 31 December 2008. METHODS: All cases receiving infliximab for ulcerative colitis or Crohn's disease over a 10-year period were identified from hospital pharmacy records. The study was based on a single centre cohort, with an unselected patient group. RESULTS: A total of 271 patients were identified as receiving infliximab for either Crohn's disease or ulcerative colitis over the 10-year study period. In total, 2169 infusions were given to the patient cohort. Fifty adverse events led to discontinuation of infliximab therapy in 47 cases. Two patients stopped due to neurological complications. There were six malignancies diagnosed within the cohort during the study period. Four of these were diagnosed while the individual was receiving Infliximab and two occurred at an interval of 21-52 months post their final infliximab infusion. A total of five deaths (1.5%) were observed during the study period. CONCLUSION: Infliximab therapy seems to be safe and efficacious in the long term. Although the development of malignancy remains a concern, we have not seen an increased risk of serious infection within our cohort.

Adherence to colorectal polyp surveillance guidelines: is there a 'scope' to increase the opportunities for screening?

Colorectal polyps are usually asymptomatic and are found opportunistically. Individuals with adenomata are at increased risk for cancer and therefore guidelines exist for surveillance of these lesions including those of the British Society of Gastroenterology (BSG). Deviation from these guidelines is common and increases the workload of endoscopy. We examined those individuals waiting for endoscopy for polyp surveillance to see whether strict adherence to BSG guidelines could facilitate opportunities for screening. A total of 413 patients with earlier colonic polyps were examined, of whom 50 patients were excluded based on having alternative indications for surveillance, 179 (49.3%) were appropriately scheduled for surveillance and 184 patients (55.9%) were scheduled incorrectly. Seventy-nine patients (30%) could have been discharged; of these, 59 had hyperplastic polyps. Of the remaining 105 inappropriate triages under surveillance at the wrong interval, seven patients were scheduled for too infrequent surveillance and 98 were too frequent. A total of 284 patients with adenomatous polyps were under surveillance of whom 11 patients (3.8%) were in the high-risk category and all were appropriately scheduled, and 75 patients (26.4%) were in the intermediate-risk category, of whom 48 were appropriately scheduled, 20 were incorrectly triaged as high risk and seven were triaged as low risk. A total of 198 (69.7%) patients were in the low-risk category, 117 of these were correctly triaged, 15 were incorrectly triaged as high risk and 66 were classified as intermediate risk. Over a five-year period, 318 unnecessary colonoscopies are being performed. On the basis of the data obtained from a population-based colorectal screening programme using immunohistochemical-faecal occult blood testing in our department another 1516 patients could be screened annually without requiring any additional endoscopy resources, if strict adherence to guidelines was assured.

Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland.

INTRODUCTION: Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES: To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD: Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS: Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION: This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.

Pylera for the eradication of Helicobacter pylori infection.

An ideal antibiotic regimen for Helicobacter pylori should achieve eradication rates of approximately 90%. Current 7-day triple therapy is successful in about two-thirds of patients. A novel treatment is required to achieve higher eradication with minimal induction of bacterial resistance. The aim of this article is to evaluate the safety and efficacy of a single triple capsule (Pylera) containing bismuth, metronidazole and tetracycline, given with omeprazole for the eradication of H. pylori infection. Extensive literature searches were conducted using PubMed data from 1982 to 2007. This search included headings of H. pylori, bismuth and eradication therapy. The triple capsule Pylera, when given with omeprazole, achieved eradication rates ranging between 84 and 97%. Eradication rates were similar for clarithromycin- and metronidazole-resistant strains. Eradication rates with an omeprazole, bismuth, metronidazole and tetracycline regimen appeared comparable for metronidazole-resistant and -sensitive strains. This effect is not seen with the use of triple therapy in cases of clarithromycin resistance. Clinical trials did not report any serious side effects from bismuth-based regimens and compliance was similar to standard triple therapy. Bismuth-based triple therapy using Pylera is a simplified, effective and well-tolerated regimen achieving cure rates of above 90%.

Helicobacter pylori eradication: role of individual therapy constituents and therapy duration.

Treatment of Helicobacter pylori (H. pylori) infection has become a key factor in the management of dyspepsia and is the treatment of choice for peptic ulcer disease. First-line eradication regimens combining a proton pump inhibitor (PPI) with clarithromycin and amoxicillin or metronidazole are considered most effective when given for a minimum period of 1 week. Eradication regimens of shorter duration have shown promising results but clinical experience remains limited. Pharmacological properties such as bioavailability and plasma concentrations of individual PPIs differ between individuals but it remains unclear whether these differences impact on the efficacy of eradication therapy and are influenced by renal or hepatic impairment. Bioavailability of PPIs also differs and is impacted on by factors including intragastric pH, metabolic pathways, potency on an mg-for-mg basis and intrinsic antibacterial activity. Several significant pharmacokinetic differences between the PPIs do not seem to influence overall H. pylori eradication rates for first-line triple therapy. However, comparison of factors including pharmacokinetics and treatment duration may prove important in achieving successful eradication with second- and third-line treatments. Based on the factors which influence therapy outcome, we suggest an algorithm for the use of H. pylori eradication therapies.

Treatment of Helicobacter pylori infection.

Antibiotic resistance has resulted in unsatisfactory eradication results with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates. Sequential therapy with amoxicillin (1 g twice a day) and a proton pump inhibitor (PPI) (twice a day) given for 5 days followed by a PPI plus clarithromycin (500 mg twice a day) and tinidazole (500 mg twice a day) for 5 days is now a first-line therapy for Helicobacter pylori in some countries. Standard triple therapy is effective in regions where clarithromycin resistance is low. Levofloxacin based triple therapy is an effective alternative to quadruple therapy in second-line treatment. Adjuvant therapy may reduce side-effects and improve compliance. Molecular and genomic research on H. pylori may result in the development of targeted antibiotic therapy; however, more research is required in this field. Further research in vaccination is also necessary before this can become an option in clinical practice.

Helicobacter pylori gastritis, the unifying concept for gastric diseases.

Helicobacter pylori infection causes a broad spectrum of clinical diseases and the clinical manifestations of the infection depend on host, environmental, and bacterial factors. These factors have an impact on the pattern and severity of gastritis and ultimately determine the clinical outcome of H. pylori infection. Better staging of gastritis may help to identify patients at risk of gastric cancer. In this article we will examine the complex interaction between host, environmental, and bacterial factors in the pathogenesis of H. pylori infection.

What therapies have replaced rofecoxib in Ireland?

AIMS: To examine prescription patterns of nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics in patients prescribed chronic rofecoxib treatment prior to withdrawal from the Irish market, and to determine the impact on proton pump inhibitor (PPI) co-prescription. METHODS: Using a national prescribing database, adults (> or =16 years) prescribed rofecoxib for > or =3 months, but not analgesics, from January to September 2004 were identified. A longitudinal prescribing history was used to determine switching patterns to other cyclooxygenase (COX)-2 inhibitors, NSAIDs or analgesics during 3 and 12 months after withdrawal. Concomitant PPI prescription was examined. Logistic regression was used to determine the likelihood of switching to a COX-2 inhibitor vs. nonselective NSAID and factors influencing concomitant PPI prescription. RESULTS: After rofecoxib withdrawal, 30.2% (1558) and 17.9% (922) of the 5155 study subjects received no further NSAID prescription during 3 and 12 months, respectively. During the 12-month period, approximately one-third of NSAID prescriptions were for <3 months; 40.7% (2096) received sequential prescriptions for different NSAIDs. Co-prescription of analgesics occurred in 49.3% (2539) of subjects. Neither age nor gender influenced the type of NSAID prescribed in the 12 months post rofecoxib withdrawal. PPI prescription increased by 5.5% during the study, associated with use of nonselective NSAIDs, prior use of PPIs and increasing age. CONCLUSIONS: The majority of those receiving chronic rofecoxib therapy were prescribed either no further NSAID or short-term NSAID therapy only during the 12 months post withdrawal, which suggests the subsequent controversy may have encouraged prescribers to adhere more closely to published guidelines.

Efficacy and safety of 6-thioguanine in the management of inflammatory bowel disease.

OBJECTIVE: 6-Thioguanine has been used as an alternative immunomodulator in the treatment of inflammatory bowel disease but data on its efficacy and safety are limited. The aim of this study was to analyse our experience of the efficacy and safety of 6-thioguanine in inflammatory bowel disease. MATERIAL AND METHODS: Patients attending the inflammatory bowel disease clinic who were started on 6-thioguanine therapy were included in this prospective observational study. Indications for initiating 6-thioguanine therapy and other related clinical, pharmacological and laboratory parameters prior to and during therapy were recorded to determine the efficacy and safety of 6-thioguanine. RESULTS: A total of 40 patients were treated with 6-thioguanine, 28 with Crohn's disease, 10 with ulcerative colitis and 2 with indeterminate colitis, at a fixed daily dose of 40 mg and continued for a median duration of 34 weeks (range 2-90 weeks). The indications for 6-thioguanine therapy included previous clinical resistance to thiopurine analogues (n=21), intolerance to thiopurine analogues (n=8) and de novo 6-thioguanine use in steroid refractory disease (n=11). Disease remission was reached in 44%, 73% and 89% of these patient groups at 3, 6 and 12 months, respectively. Inflammatory markers and steroid use were significantly lower during 6-thioguanine therapy compared with in the period before therapy. Therapy was discontinued in 13 patients (33%), mainly because of thrombocytopenia and associated hepatotoxicity. CONCLUSIONS: 6-Thioguanine is a useful addition to treatment in inflammatory bowel disease but the frequent occurrence of hepatotoxicity limits its routine use.

Eradication of Helicobacter pylori: recent advances in treatment.

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.

Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients.

BACKGROUND: Optimal management approach is not well defined for subjects who fail initial first- and second-line Helicobacter pylori eradication attempts and are dealt on a case-by-case basis by the specialists. AIM: To evaluate the efficacy and safety of standard and 'rescue' eradication therapies at primary and secondary care levels. METHODS: H. pylori infected dyspepsia patients referred to our C13 urea breath testing laboratory between January 1999 to February 2002 were included. Eradication failure at secondary care level was treated using strategies including antibiotic sensitivity testing and the use of rifabutin- and furazolidone-based therapies. RESULTS: 3280 patients received standard first-line eradication therapy, which was successful in 2530 (77%) patients. Second-line therapy (bismuth-based 'quadruple') or triple therapy (altering constituent antibiotics) was successful in 56% of 270 treated patients. Subsequent eradication attempts using rifabutin-based (n = 34) and furazolidone-based (n = 10) regimens were successful in 38% and 60% patients respectively. H. pylori eradication rates were significantly different for guidelines compliant (94.8%) and non-compliant (82%) groups (P = 0.0001). H. pylori eradication rates for non-ulcer dyspepsia (40%) and peptic ulcer disease (36%) were not significantly different. CONCLUSIONS: Available H. pylori eradication therapies remain very effective and compliance to guidelines achieves high success rates. Furazolidone-based 'rescue' regimen achieved high eradication rates after failure of the standard first-line, second-line and rifabutin-based therapies.

Argon plasma coagulation as first-line treatment for chronic radiation proctopathy.

BACKGROUND AND AIM: Chronic radiation proctopathy is a troublesome complication of radiotherapy to the pelvis, for which current treatment modalities are unsatisfactory. The present prospective study was designed to determine the usefulness and safety of argon plasma coagulation in the management of chronic radiation proctopathy. METHODS: Twenty-five consecutive patients (M:F 24:1, mean age: 69 years) with radiation proctopathy were prospectively included. All patients received argon plasma coagulation by a standard protocol. Response to treatment was assessed by symptom response, bleeding severity score, hematological parameters and transfusion requirements over a median 14-month follow up. RESULTS: Patients received a median of one treatment session with argon plasma coagulation. There was significant improvement in rectal bleeding in all patients, with complete cessation of bleeding in 21 (81%) of the patients. The median bleeding severity score fell from 3 to 0 (P < 0.0005). The mean hemoglobin level rose from 10.05 +/- 2.21 g/dL before treatment to 12.44 +/- 1.09 g/dL at 6 months following treatment (P < 0.002). There was also improvement in other symptoms such as urgency and diarrhea. Over the period of follow up, there was no recurrence of anemia and no complications were noted. CONCLUSION: These results suggest that argon plasma coagulation is a safe and effective modality in the treatment of chronic radiation proctopathy.

Therapy of Helicobacter pylori.

This represents an overview of the main data published over the last year on the therapy of Helicobacter pylori. The problem of increasing failure of H. pylori eradication has been the main focus, with increasing resistance and poor patient compliance being the main culprits. Simple regimens are necessary to improve patient compliance. New antibiotics and novel agents are appraised with mixed results.