Theodore Rokkas

Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report

Background: Guidelines on the management of Helicobacter pylori, which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in (a) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; (b) patients with atrophic gastritis; (c) first degree relatives of patients with gastric cancer; (d) patients with unexplained iron deficiency anaemia; and (e) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a “test and treat” strategy if other causes are excluded. Eradication of H pylori infection (a) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and (b) may prevent peptic ulcer in patients who are naïve users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease

A close relationship has been found between Helicobacter pylori and peptic ulcer disease. Furthermore, eradication of H. pylori is associated with low recurrence rates. The aim of the present study was to examine whether eradication of H. pylori has any impact on the complications of ulcers, such as bleeding. Thirty-one patients hospitalized for duodenal ulcer bleeding, undergoing conservative treatment and with a previous history of bleeding, comprised the group studied. All patients had emergency endoscopy, and tests for H. pylori proved to be positive in all. After discharge, patients were given omeprazole 20 mg daily for 4 weeks for ulcer healing, which was achieved in all patients (100%). After this, patients were randomized to receive either omeprazole 20 mg t.i.d. alone (group O, n = 15) or the combination of omeprazole 20 mg t.i.d. + amoxicillin 500 mg q.i.d. (group O + A, n = 16) for 2 weeks. Endoscopy was performed 4 weeks after treatment ended to check for eradication of H. pylori and again when rebleeding or symptomatic relapse occurred. Groups O and O + A were similar in age, sex, smoking habits, and NSAID use. The follow-up period was 12 months for both groups. Eradication was achieved in 2 of 15 (13.3%) patients in group O and in 13 of 16 (81.3%) patients in group O + A (p < .001). Five patients rebled during follow-up. All of them belonged to group O and were patients in whom eradication had failed. In contrast, none of group O + A had rebleeding (p = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Does Purgative Preparation Influence the Diagnostic Yield of Small Bowel Video Capsule Endoscopy?: A Meta-Analysis

OBJECTIVES:Video capsule endoscopy (VCE) is a useful tool in investigating small bowel pathology. However, the role of bowel preparation is controversial. Therefore, the aim of this study was to explore the role of bowel preparation and in particular its consequences on diagnostic yield in a meta-analysis of all relevant studies.METHODS:Extensive English-language medical literature searches were performed up to February 2008, using suitable keywords, looking for human studies that compared different modes of small bowel preparation (purgative vs. clear liquids diet). We examined the effects of this preparation on the following three primary end points, diagnostic yield (DY), small bowel visualization quality (SBVQ), and VCE completion rate (CR) by meta-analysis of relevant studies.RESULTS:A total of 12 eligible studies (6 prospective, 6 retrospective) were identified, including 16 sets of data relevant to our primary end points. There were significant differences between patients prepared with purgative vs. those prepared with clear liquids diet in DY (263 vs. 213 patients, respectively; OR (95% CI)=1.813 (1.251–2.628), P=0.002) and SBVQ (404 vs. 249 patients, respectively; OR (95% CI)=2.113 (1.252–3.566), P=0.005). There was no statistically significant difference regarding CR rate. Purgatives did not affect VCE gastric transit time (GTT) or VCE small bowel transit time (SBTT).CONCLUSIONS:Pooled data showed that in comparison to clear liquids diet, purgative bowel cleansing, before VCE, improves the SBVQ and increases the DY of the examination, but does not affect the VCE completion rate.

Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis.

Despite the fact that the association ofHelicobacterpylori with an increased risk of gastriccancer is well documented, the exact mechanisms of thisassociation have not been elucidated. Our aim was to shed some light on these mechanisms by studyingThe relationship of H. pylori CagA status to gastriccell proliferation and apoptosis, since both play animportant role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fiftypatients [32 men, 18 women, median age 39.5 years (range18-67)], referred for upper gastrointestinal endoscopy,from whom antral biopsies were taken. On biopsy specimens gastritis was estimated byscoring the severity of inflammatory infiltrate, and thepresence of atrophy and intestinal metaplasia were alsonoted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelialapoptotic index (AI) was measured by special stainingfor apoptosis, and CagA status was determinedserologically by immunoblotting the sera of patientsagainst H. pylori antigens. Thirty-eight (76%) of the50 patients were H. pylori (positive) and 12 (24%) H.pylori (negative). Among the 38 H. pylori (+) patients,28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups,the PI values [median (ranges)] were 5 (4-7) and 3.7(3.5-5.5), respectively (P < 0.05). In addition thedifference in PI between the H. pylori CagA(+) and H. pylori (-) groups was highly significant (P< 0.001). Concerning apoptosis, in the H. pyloriCagA(+) and CagA(-) groups, the values for AI were 1(1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between theH. pylori CagA(-) and H. pylori (-) groups, wassignificant (P < 0.05). We conclude that H. pyloriCagA(+) strains induce increased gastric cellproliferation, which is not accompanied by a parallel increasein apoptosis. This might explain the increased risk forgastric carcinoma that is associated with infection byH. pylori CagA(+) strains.

Gastric phytobezoars may be treated by nasogastric Coca- Cola lavage

Large gastric phytobezoars may occur in patients with gastric dysmotility disorders. Treatment options include dissolution with enzymes, endoscopic fragmentation with removal or aspiration, and surgery. We report our experience with nasogastric cola lavage therapy. Over an 8-year period, five consecutive patients were referred to our unit for endoscopic treatment of large gastric phytobezoars. They included one patient with lobectomy for lung cancer and four patients with diabetic gastroparesis. An initial attempt of endoscopic fragmentation and removal was unsuccessful. Patients were treated with 3 l of Coca-Cola nasogastric lavage over 12 h. Nasogastric lavage was very well tolerated by the patients. Complete phytobezoar dissolution was achieved in one session in all cases. There were no procedure-related complications. The dissolution of large gastric phytobezoars with cola nasogastric lavage is a safe, rapid and effective method. Patients may be treated in the medical ward, avoiding therapeutic endoscopy or surgery.

The role of video capsule endoscopy in the diagnosis of celiac disease: a meta-analysis.

Background Video capsule endoscopy (VCE) is an attractive and patient friendly tool that provides high quality images of the small bowel. The reported yield of VCE in diagnosing celiac disease (CD) has shown variable results. Objective The aim of this study was to assess the accuracy of VCE by pooling data of existing trials. Design Meta-analysis. The fixed-effects or random-effects model was used as appropriate, based on whether homogeneity or heterogeneity, respectively, was indicated by the Cochran Q-test. Patients Studies that estimated the accuracy of VCE were identified. The two investigators independently conducted the search and data extraction. A total of 166 individuals were included in this meta-analysis. Methods An extensive literature search was performed and studies that estimated the accuracy of VCE in CD were identified. The two investigators independently conducted the search and data extraction. Data from the eligible studies were collected and pooled; sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were computed. In addition, the results of the individual studies were displayed in a receiver operating characteristic (ROC) space to illustrate the distribution of sensitivities and specificities. A weighted symmetric summary ROC curve was computed and the area under the curve (AUC) was calculated, with perfect tests having an AUC of 1 and poor tests having an AUC close to 0.5. Results Out of 461 titles initially generated by the literature searches, six studies met the inclusion criteria and were eligible for meta-analysis. The overall pooled VCE sensitivity was 89% [95% confidence interval (82–94%)] and specificity was 95% [95% confidence interval (89–98%)]. The AUC under the weighted symmetric summary ROC was 0.9584. Conclusion The results of this meta-analysis mean that VCE, although it is not as accurate as pathology, could be a reasonable alternative method of diagnosing CD. Hopefully, this method will expand the portfolio of diagnostic methods available, especially in patients unwilling to undergo gastroscopy because of its perceived inconvenience and discomfort. However, larger, multicenter, and well-designed trials are needed to further establish the role of VCE in the diagnosis of CD.

Gastric Cancer: Epidemiologic Aspects

A multifactorial and multistep model of gastric cancer (GC) is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published on the relative contribution of genetic and environmental factors. Large meta‐analyses confirmed the association between IL8, IL10, TNF‐b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk. Several microRNAs have also been associated with GC and their prognosis. Cohort studies have shown the association between GC and fruit, flavonoid, total antioxidant capacity, and green tea intake. Obesity was associated with cardia GC, heme iron intake from meat with GC risk. Several large meta‐analyses have confirmed the positive association of GC with salt intake and pickled foods and the negative association with aspirin use.

Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: a meta-analysis.

Objectives Helicobacter pylori (H. pylori) is believed to predispose to gastric cancer by inducing the precancerous changes, that is, atrophy and intestinal metaplasia (IM). First-degree relatives of patients with gastric cancer might be at an increased risk of developing gastric cancer. However, this evidence is based on the scattered individual studies. The aim of this study was to examine the risk of first-degree relatives developing gastric cancer, in comparison with controls that have no family history of gastric cancer, by meta-analyzing all relevant studies. Methods Extensive English language medical literature searches for human studies were performed up to the end of November 2009, using suitable keywords. Inclusion and exclusion criteria were identified and in eligible studies data on three parameters, that is, H. pylori prevalence, atrophy and IM, were extracted. Pooled estimates (odds ratio with 95% confidence intervals) were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Eggers regression asymmetry test. Results Out of 155 initially identified studies, 11 studies, from various countries, fulfilling the inclusion criteria, examined the risk of first-degree relatives developing gastric cancer (n=1500) in comparison with controls (n=2638). For H. pylori prevalence, the pooled odds ratio with 95% confidence interval was 1.925 (1.419–2.611) and the test for overall effect Z was 4.211 (P=0.000). The respective values for atrophy and IM were 2.200 (1.266–3.824), Z=2.797, (P=0.005) and 1.982 (1.363–2.881), Z=3.582 (P=0.000) respectively. Conclusion The results of this meta-analysis showed that first-degree relatives of patients with gastric cancer might be at an increased risk of developing gastric cancer, as judged by significantly higher prevalence of H. pylori, gastric atrophy and IM, in comparison with controls. Consequently, H. pylori detection and prophylactic eradication of the infection should be offered to such individuals. However, follow-up studies are required to prove the above.

Helicobacter pylori: the challenge in therapy.

For the therapeutic management of Helicobacter pylori infection, the Maastricht 2–2000 Consensus Report have introduced the concept of the ‘treatment package’ that considers first‐ and second‐line eradication therapies together. According to this consensus statement, the first‐line therapy for H. pylori eradication is a combination of the proton pump inhibitors (PPI) or ranitidine bismuth citrate (RBC) and claritromycin plus either amoxicillin or metronidazole. The second‐line treatment is suggested to be PPI‐quadruple therapy for a minimum of 7 days. If bismuth compounds are not available, PPI‐based triple therapy will have to be used as a second‐line treatment only after susceptibility testing. Since no considerable progress has been made during the past year in treatment regimens, there is still a need for new compounds that are specific for H. pylori, which could constitute future therapies.