Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

AIM: To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. METHODS: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. RESULTS: Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. CONCLUSIONS: Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids.

Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori.

BACKGROUND: Up-to-date information regarding the recurrence rate of Helicobacter pylori (H. pylori) after eradication therapy is not available. AIM: To evaluate the global recurrence rate following H. pylori eradication therapy and confirm its association with socioeconomic and sanitary conditions. METHODS: A systematic search of PubMed, EMBASE and the Cochrane library was performed to identify potentially relevant publications using the following keywords: "Helicobacter pylori" or "H. pylori" or "Hp" and "recurrence" or "recrudescence" or "reinfection" or "recurrent" or "recurred" or "re-infect*" or "relapse*." RESULTS: A total of 132 studies (53 934 patient-years) were analysed. Each study was weighted according to the duration of patient-years. The global annual recurrence, reinfection and recrudescence rate of H. pylori were 4.3% (95% CI, 4-5), 3.1% (95% CI, 2-5) and 2.2% (95% CI, 1-3), respectively. The H. pylori recurrence rate was inversely related to the human development index (HDI) (ie, 3.1% [95% CI, 2-4], 6.2% [95% CI, 4-8] and 10.9% [95% CI, 6-18] in countries with a very high, high and medium or low HDI) (P <.01) and directly related to H. pylori prevalence (10.9% [95% CI, 7-16], 3.7% [95% CI, 3-5], 3.4% [95% CI, 2-5] and 1.6% [95% CI, 0.5-3] in countries with a very high, high, medium or low local H. pylori prevalence) (P <.01). Global recurrence rates remained relatively stable between 1990s, 2000s and 2010s but varied across different regions (P <.05). CONCLUSIONS: H. pylori recurrence remains a problem closely associated with socioeconomic and sanitary conditions. Methods to reduce recurrence in developing countries are needed.

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.

Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study.

BACKGROUND: Intestinal-type gastric cancer (GC) still ranks among the high-incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy-based) ranking of GC risk. AIM: To test the gastritis OLGA-staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression. METHODS: Ninety-three Italian patients were followed up for more than 12 years (range: 144-204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow-up (T2). RESULTS: All invasive or intra-epithelial gastric neoplasia were consistently associated with high-risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA-staging at T1 predicted both the OLGA stage (Kaplan-Maier log-rank test, P = 0.001) and the neoplasia at T2 (Kaplan-Maier log-rank test, P = 0.001). CONCLUSIONS: This long-term follow-up study provides the first evidence that gastritis OLGA-staging conveys relevant information on the clinico-pathological outcome of gastritis and therefore for patient management. According to OLGA-staging and H. pylori-status, gastritis patients could be confidently stratified and managed according to their different cancer risks.

Prospective, randomized, pathologist-blinded study of disposable alligator-jaw biopsy forceps for gastric mucosal biopsy.

BACKGROUND: Endoscopic biopsy forceps differ in the size and shape of the biopsy cup and the presence or absence of a needle. METHODS: We compared four different "large cup" forceps (three with needles) designed for 2.8mm biopsy channels. A gastric antral and corpus biopsy were obtained with each. Parameters examined included: weight (mg), length (mm), orientation (poor, good), intactness (1, 2, or 3 pieces), depth (superficial, above muscularis mucosae, included muscularis mucosae), crush artefact (yes, no), and overall adequacy (inadequate, suboptimal, adequate). RESULTS: Twenty-four patients were enrolled (191 biopsies). The median length was approximately 5mm (range 1.1-8.2mm). Histologically inadequate specimens were present in 4% with the forceps without needle compared to 16% of those with needles (P=0.061) and there were significantly fewer specimens in three or more pieces than did the forceps with needles 2.1% vs. 12.6% (P<0.05). CONCLUSIONS: Current alligator style forceps provide a high proportion of acceptable specimens with only minor differences between brands. Forceps from one source were least preferred by endoscopy assistants and had the highest rates of inadequate biopsies and biopsies with crush artefact. Forceps without needles provide histologically acceptable samples slightly more frequently than those with needles.

Gastritis, dyspepsia and peptic ulcer disease.

Peptic ulcer disease remains a common problem and it most frequently due to the presence of an Helicobacter pylori infection or use of non-steroidal anti-inflammatory drugs (NSAIDs). Dyspepsia is neither sensitive or specific for diagnosing peptic ulcer disease. The approach to patients with dyspepsia is to arrive at a definitive diagnosis without unnecessary exposure to invasive or costly diagnostic procedures. Non-invasive testing is preferred with endoscopy being reserved for those with alarm markers or above a specified age (e.g., 55 years in Western countries). Patients negative for H. pylori infection should receive an empiric trial of acid suppression for 4 to 8 weeks and if beneficial it can be continued.

Gastric endoscopy in the 21st century: appropriate use of an invasive procedure in the era of non-invasive testing.

BACKGROUND: The acceptance of the premise that Helicobacter pylori infection is aetiologically related to gastric cancer and peptic ulcer and that the risk of gastric cancer among Helicobacter pylori infected individuals is related to the extent, severity and duration of atrophic gastritis has led to major changes in medical and endoscopic practices. The development of non-invasive methods to detect Helicobacter pylori and to estimate the extent and severity of gastritis has reduced the need for diagnostic endoscopy in asymptomatic individuals. METHODS AND RESULTS: Here we provide recommendations regarding deciding whether non-invasive and endoscopic assessment of the gastric mucosa is preferred. We also include specific recommendations and caveats regarding the preferred biopsy number and sites as well as the identification of specimens, to allow the pathologist to reliable stage the severity and extent of gastritis, and thus provide prognostic information needed for patient managements (e.g., whether endoscopic surveillance is recommended). CONCLUSION: In summary, while there is clearly a role for gastric endoscopy and endoscopic biopsy in the Helicobacter pylori era, obtaining useful diagnostic and prognostic information is critically dependent upon attention to detail with regard to biopsy site and identification as to the location from where the specimen was taken.

Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines.

BACKGROUND: Helicobacter pylori remains a global health hazard, and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful. METHODS: In two prospective, randomised, double-blind, controlled studies (Paul Ehrlich Institute application nos 0802/02 and 1097/01), live vaccines against H pylori were tested in human volunteers seronegative for, and without evidence of, active H pylori infection. Volunteers (n = 58) were immunised orally with Salmonella enterica serovar Typhi Ty21a expressing H pylori urease or HP0231, or solely with Ty21a, and then challenged with 2x10(5) cagPAI(-) H pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and postchallenge. Infection was terminated with antibiotics. RESULTS: Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H pylori (5/13) completely or reduced the H pylori burden (8/13). H pylori-specific T helper cells were detected in 9 of these 13 (69%), but only in 6 of 45 (13%) breath test-positive volunteers (p = 0.0002; Fisher exact test). T cells were either vaccine induced or pre-existing, depending on the volunteer. CONCLUSION: Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell-mediated immunity against H pylori infection in humans.

OLGA staging for gastritis: a tutorial.

Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for (intestinal-type) gastric cancer development and the extent/topography of the atrophic changes significantly correlates with the degree of cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. The histology report consequently does not give clinical practitioners and gastroenterologists an explicit message of use in orienting an individual patient's clinical management. Building on current knowledge of the biology of gastritis and incorporating experience gained worldwide by applying the Sydney System for more than 15 years, an international group of pathologists (Operative Link for Gastritis Assessment) has proposed a system for reporting gastritis in terms of stage (the OLGA staging system). Gastritis staging arranges the histological phenotypes of gastritis along a scale of progressively increasing gastric cancer risk, from the lowest (stage 0) to the highest (stage IV). This tutorial aims to provide unequivocal information on how to consistently apply the OLGA staging system in routine diagnostic histology practice.