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.

Motion--Helicobacter pylori worsens GERD: arguments for the motion.

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease-free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.

Immunochemical faecal occult blood tests have superior stability and analytical performance characteristics over guaiac-based tests in a controlled in vitro study.

AIMS: The aims of this study were (1) to determine the measurement accuracy of a widely used guaiac faecal occult blood test (gFOBT) compared with an immunochemical faecal occult blood test (iFOBT) during in vitro studies, including their analytical stability over time at ambient temperature and at 4°C; and (2) to compare analytical imprecision and other characteristics between two commercially available iFOBT methods. METHODS: Faecal specimens from healthy volunteers negative for occult blood were spiked with red cell lysate to give concentrations of 0 (A), 2.5 (B) and 4.5 (C)1mg Hb/g faeces respectively. Samples from each pool were then tested by nine blinded assessors in order to determine the measurement accuracy. Sample stability for the gFOBT at ambient temperature (18°C) was determined by repeating the gFOBT analysis on faecal samples (A, B and C) consecutively for 7 days. Stability for the iFOBT was tested on spiked faecal samples stored at 4°C and also at ambient temperature (18°C). Testing for other analytical performance characteristics including sample carryover and imprecision was performed for both iFOBT methods. RESULTS: Nine blinded assessors using gFOBT achieved correct readings for eight of nine samples from Pool A, five of nine from Pool B and seven of nine from Pool C. Overall, the sensitivity and specificity of gFOBT were 67% and 89% respectively. No discrepant results were detected with iFOBT. Faecal samples applied to gFOBT cards immediately postcollection gave positive results for the next 7 days only for pool C. In contrast, the results of iFOBT remained stable up to 14 days at 18°C. The within-run imprecision and sample carryover showed robust results with both iFOBT methods. CONCLUSIONS: The superior analytical stability and measurement accuracy demonstrated by the iFOBT in this in vitro study confers advantages over traditional qualitative gFOBTs and supports their suitability for more widespread use in population-based colorectal-cancer screening programmes.

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.

Primary prevention of colorectal cancer: are we closer to reality?

Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.

The long-term risk of continuous immunosuppression using thioguanides in inflammatory bowel disease.

The efficacy of thiopurine treatment in the induction, and especially maintenance, of remission in inflammatory bowel disease is well proven; however, it is associated with side effects in both medium and long-term use. The potential harmful effects may be anticipated and minimised by due diligence prior to commencing these drugs followed by close monitoring of haematological and biochemical parameters once started. Careful clinical examination and history taking are also essential. Affected patients are expected to lead lives that include travel, employment and pregnancy - the implications of continued thiopurine therapy in such patients are discussed.

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.

Colonic adenoma patients have higher incidence of hyperplastic polyps on surveillance colonoscopy.

OBJECTIVES: To determine the incidence of hyperplastic polyps in patients undergoing surveillance colonoscopy and to compare with the prevalence in individuals undergoing index colonoscopy. PATIENTS AND METHODS: This prospective observational study included patients with index colonoscopy findings of adenomas, adenoma with concomitant hyperplastic polyps and advanced neoplasia who subsequently underwent surveillance colonoscopy. Patient characteristics, indications for colonoscopy, interval between examinations and findings were recorded. These findings were compared with our control group that comprised of patients who underwent index colonoscopy during the same period. RESULTS: Study group consisted of 108 patients (median age 61.5 years) who underwent index colonoscopy for indications including, weight loss, rectal bleeding, altered bowel habits and anaemia. On index colonoscopy, adenomas, adenoma with concomitant hyperplastic polyps and advanced neoplasia were present in 61, 35 and 12 patients, respectively. Surveillance colonoscopy was performed after a mean follow-up period of 29 +/- 17 months. Findings on surveillance examination included hyperplastic polyps in 35 and 57% of patients with past adenomas and adenoma with concomitant hyperplastic polyps, respectively. Control group included 3852 symptomatic patients who had index colonoscopy (median age, 65 years). Hyperplastic polyps, adenomas and advanced neoplasia were found in 155 (4%), 388 (10%) and 60 (1.5%) of patients, respectively. Hyperplastic polyps and adenoma were significantly higher in study group as compared with control group (P >0.5). CONCLUSION: Incidence of hyperplastic polyps is significantly higher on surveillance colonoscopy as compared with the prevalence on index colonoscopy. This may signify a continuous spectrum of biological evolution between hyperplastic polyps and adenomas.

Concept of chemoprevention in colorectal cancer.

Colorectal cancer remains a significant cause of morbidity and mortality throughout the world. The incidence of colorectal cancer is nearly four-fold higher in more-developed as compared with less-developed regions of the world. At present an early detection of colorectal cancer remains a crucial step in determining the therapeutic outcomes. Screening programmes have been introduced in an effort to detect colorectal cancer at an early stage or at a precancerous colonic polyp stage. These programmes should be used by the health professionals as an opportunity to educate the public regarding the use of chemoprevention in colorectal cancer, which is the main focus of this review and an attractive concept needing further evaluation.

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.

Clinical conditions and patient factors significantly influence diagnostic utility of D-dimer in venous thromboembolism.

Determining D-dimer levels remains important in the diagnostic algorithms for venous thromboembolism (VTE). The present study aimed to identify factors influencing D-dimer utility in diagnosing VTE. Consecutive symptomatic medical patients, who attended our emergency department from 1 November 2006 to 31 December 2006, had D-dimer levels measured as fibrinogen equivalent units (FEU), following clinical risk assessment. Diagnosis of VTE was established by venous compression ultrasonography and computed tomographic pulmonary angiography. VTE-negative patients were followed for 2 months to detect future occurrence of thromboembolism. Impact of various factors on D-dimer levels was analyzed. Four thousand and twenty-six patients attended our emergency department, and 525 patients (median age 52 years) had D-dimer assessed. Final diagnosis of VTE was established in 25 (4.7%) patients on radiological investigations. Median D-dimer levels for VTE-negative patients less than 60 years old, with normal renal function and chest radiology were 0.38 microgFEU/ml (range 0.19-2.3), 0.39 microgFEU/ml (range 0.17-3.5) and 0.39 microgFEU/ml (range 0.1-4.3), respectively. Similar figures for those at least 60 years, with renal impairment and abnormal chest radiology, were 0.75 microgFEU/ml (range 0.22-4.3), 0.52 microgFEU/ml (range 0.17-4.4) and 0.92 microgFEU/ml (range 0.26-5.6), respectively. Factors including patient age, renal function and chest radiology had significant influence on D-dimer levels (P < 0.01). A triad of patient age at least 60 years, renal impairment (modification of diet in renal disease stage 2-5) and abnormal chest radiology had a false positive D-dimer in 96% of patients (n = 72). Use of D-dimer in patients with a triad of advanced age, renal impairment and abnormal chest radiology has no practical diagnostic value in VTE.

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%.

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.

Treatment of Helicobacter pylori infection.

Review of the recently published data on Helicobacter pylori management highlights various interesting aspects. Current H. pylori eradication guidelines generally suggest a noninvasive 'test and treat' strategy for all dyspeptic patients with certain age limits depending on the local gastric neoplasia risk. According to the 'Maastricht 2-2000 Consensus Report' treatment should be thought of as a 'package' considering first- and second-line eradication therapies together. Various centres have published their results using novel antimicrobial formulations and 'rescue' and 'sequential' therapies. Review suggests that care at the specialist level remains a challenge and guidelines are deficient particularly as regards the selection and duration of eradication therapies. Results indicate that differences for CYP2C19 genotype and the selection of proton pump inhibitors have no significant role in determining eradication rates whereas antibiotic resistance and socio-economic factors play a variable role according to different geographical areas. Compliance remains an important factor in determining clinical outcome at the primary and secondary levels worldwide.