Summary
Helicobacter pylori infection is a major cause of morbidity and mortality worldwide. More than 50% of the global population is estimated to be infected.
Differences in prevalence exist within ...and between countries, with higher prevalence seen among people with lower socio‐economic status.
Most transmission of infection occurs early in life, predominantly from person to person in the family setting.
H. pylori is the cause of most peptic ulcer disease, gastric cancer and gastric mucosa‐associated lymphoid tissue (MALT) lymphoma and causes symptoms in a subset of patients with functional dyspepsia.
Choice of diagnostic test depends on the clinical context; urea breath tests and endoscopy with biopsy are the major diagnostic tools.
Evidence‐based indications for eradication of H. pylori infection are well documented.
The most widely used and recommended eradication therapy in Australia is triple therapy comprising a proton pump inhibitor, amoxycillin and clarithromycin, usually for 1 week. Effective alternative regimens are available for patients with proven allergy to penicillin.
Antimicrobial resistance is the major determinant of the outcome of eradication therapy. Trends in antibiotic resistance need to be monitored locally, but individual patient susceptibility testing is not usually necessary as it rarely guides the choice of therapy.
The outcome of treatment should be assessed not less than 4 weeks after therapy. This is usually done with a urea breath test if follow‐up endoscopy is not required.
When first‐line therapy fails, several proven second‐line therapies may be used. Repeat first‐line therapy and ad hoc regimens should be avoided. Overall cumulative eradication rates should approach 99%.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is ...recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps.
We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps.
Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies.
Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls ...disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.
Background
First‐line Helicobacter pylori eradication failure is a common and challenging problem.
Aim
To assess the efficacy of salvage levofloxacin‐based triple therapy in Australia.
Methods
...Prospective patients referred after prior treatment failure(s) were prescribed esomeprazole 40 mg, amoxicillin 1 g and levofloxacin 500 mg each twice daily for 10 days. All patients received detailed written and verbal adherence support. Outcome assessment was by
13C‐urea breath test and/or histology and urease test.
Results
In 150 consecutive, evaluable patients (66% female, mean age 54 ± 14 years; six smokers), the main indications for treatment were peptic ulcer disease (17%), increased gastric cancer risk (20%), symptoms (35%) and other risk reduction (28%). The median number of previous treatments was 2 (range 1–7). Eradication of H. pylori was achieved in 90% (intention to treat (ITT)) and 91% (per‐protocol (PP)) of patients. The eradication rate did not differ according to the type or number of prior treatments: 93% when ≤2 (n = 107) compared with 84% after three or more prior treatments (n = 43; P = 0.13) or with age, ethnicity or indication for treatment but it was higher in females (ITT 94 vs 82%, P = 0.04). Adherence was excellent (95%). No serious adverse effects were observed; mild adverse effects were reported in 11%. No primary levofloxacin resistance was observed in 20 concurrent cases.
Conclusion
The efficacy and safety of this levofloxacin‐based triple therapy suggests it should be used as a salvage regimen in this region. Randomised comparative trials are unlikely to be done but these data compare favourably with local data for other salvage therapies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background & Aims Inflammatory bowel diseases (IBDs) increase the risk of colorectal cancer. Surveillance colonoscopy with chromoendoscopy is recommended, but conventional forward-viewing colonoscopy ...(FVC) detects dysplasia with low levels of sensitivity. Full-spectrum endoscopy (FUSE) incorporates 2 additional lateral cameras to the forward camera of the colonoscope, allowing endoscopists to view behind folds and in blind spots, which might increase dysplasia detection. We compared FUSE vs FVC in the detection of dysplasia in patients with IBDs. Methods We performed a prospective, randomized, cross-over, tandem colonoscopy study comparing FVC vs FUSE in 52 subjects with IBD undergoing surveillance for neoplasia in Australia (23 with Crohn’s colitis, 29 with ulcerative colitis; median age, 45.0 y; 60% male; mean IBD duration, 16.4 y). All subjects met national IBD surveillance inclusion criteria; 27 were assigned randomly to groups that underwent FVC followed by FUSE, and 25 were assigned to groups that underwent FUSE followed by FVC. All procedures were performed from February 2014 through December 2015. Random biopsy specimens were collected and visible lesions were collected; all were analyzed histologically. The primary end point was dysplasia missed by the first colonoscopy detected by the second colonoscopy. Dysplasia was diagnosed by an expert gastrointestinal pathologist blinded to the colonoscope allocation in consensus with a second expert pathologist. Results FVC missed 71.4% of dysplastic lesions per lesion whereas FUSE missed 25.0% per lesion ( P = .0001); FVC missed 75.0% of dysplastic lesions per subject and FUSE missed 25.0% per subject ( P = .046). FUSE identified a mean of 0.37 dysplastic lesions and FVC identified a mean of 0.13 dysplastic lesions ( P = .044). The total colonoscopy times were similar (21.2 min for FUSE vs 19.1 min for FVC; P = .32), but withdrawal time was significantly longer for FUSE (15.8 min) than for FVC (12.0 min) ( P = .03). Correcting for per-unit withdrawal time, the mean dysplasia miss rate per subject was significantly lower for FUSE (0.19) than for FVC (0.83; P < .0001). Targeted tissue acquisition identified significantly more dysplastic lesions than random biopsies ( P < .0001). Conclusions In a prospective cross-over study of IBD patients undergoing surveillance colonoscopy, we found panoramic views obtained by full-spectrum endoscopy increased the number of dysplastic lesions detected, compared with conventional forward-viewing colonoscopy. Trial no: ACTRN12616000047493.
The Asia–Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional ...guidelines. The group recognized that in addition to long‐established indications, such as peptic ulcer disease, early mucosa‐associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long‐term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population ‘test and treat’ strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long‐term aspirin or non‐steroidal anti‐inflammatory drug therapy in patients at high risk for ulcers and ulcer‐related complications. In Asia, the currently recommended first‐line therapy for H. pylori infection is PPI‐based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth‐based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI‐based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first‐line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth‐based quadruple therapy; (iii) levofloxacin‐based triple therapy; and (iv) rifabutin‐based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To determine whether once-daily esomeprazole 40 mg or 20 mg compared with placebo reduces the incidence of peptic ulcers over 26 weeks of treatment in patients taking low-dose acetylsalicylic acid ...(ASA) and who are at risk for ulcer development.
Multinational, randomised, blinded, parallel-group, placebo-controlled trial.
Cardiology, primary care and gastroenterology centres (n=240).
Helicobacter pylori-negative patients taking daily low-dose ASA (75-325 mg), who fulfilled one or more of the following criteria: age ≥18 years with history of uncomplicated peptic ulcer; age ≥60 years with either stable coronary artery disease, upper gastrointestinal symptoms and five or more gastric/duodenal erosions, or low-dose ASA treatment initiated within 1 month of randomisation; or age ≥65 years. All patients were ulcer-free at study entry.
Once-daily, blinded treatment with esomeprazole 40 mg, 20 mg or placebo for 26 weeks.
The primary end point was the occurrence of endoscopy-confirmed peptic ulcer over 26 weeks.
A total of 2426 patients (52% men; mean age 68 years) were randomised. After 26 weeks, esomeprazole 40 mg and 20 mg significantly reduced the cumulative proportion of patients developing peptic ulcers; 1.5% of esomeprazole 40 mg and 1.1% of esomeprazole 20 mg recipients, compared with 7.4% of placebo recipients, developed peptic ulcers (both p<0.0001 vs placebo). Esomeprazole was generally well tolerated. Conclusions Acid-suppressive treatment with once-daily esomeprazole 40 mg or 20 mg reduces the occurrence of peptic ulcers in patients at risk for ulcer development who are taking low-dose ASA. Clinical trial registration number ClinicalTrials.gov identifier: NCT00441727.
Thiopurines effectively maintain remission in ulcerative colitis patients. Whether early initiation of thiopurines after ulcerative colitis diagnosis decreases proximal disease progression and ...colectomy rates is not known.
We conducted a cohort study of ulcerative colitis subjects recruited from 1970 to 2009. Early thiopurine maintenance was defined as commencement of azathioprine or mercaptopurine within 5 years of diagnosis and maintenance for at least 6 months. Propensity score matching was conducted to correct for confounders influencing early thiopurine introduction. Outcomes of interest were colectomy rate and endoscopic proximal disease extension.
982 consecutive ulcerative colitis subjects (12 879 patient-years) were recruited with 116 requiring colectomy. Thiopurines initiation and maintenance increased over time with median time to thiopurine commencement decreasing from 23 years in the first decade to 2 years in the last decade (P < 0.0001). Multivariate analysis showed that early thiopurine maintenance significantly decreased the need for colectomy hazard ratio, 0.13; 95% confidence interval (CI):0.03-0.55; P = 0.006. The number of subjects needed to be treated to reduce one colectomy at 5 and 10 years was 18 (95% CI, 16- 36) and 12 (95% CI, 11-25). After propensity score matching, early thiopurine maintenance was significantly associated with decreased colectomy (hazard ratio, 0.10; 95% CI, 0.03-0.43; P = 0.002) and proximal progression of disease extent (hazard ratio, 0.26; 95% CI, 0.10-0.78; P = 0.015).
Early thiopurine maintenance for >6 months is significantly associated with reduced colectomy and proximal progression of disease extent in ulcerative colitis.
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