The management of endoscopic retrograde cholangio- pancreatography-related infections risk: results of an italian survey at regional level.

Background and aim: Among the Endoscopic retrograde cholangiopancreatography (ERCP) adverse events, an increasingly arising problem is the transmission of Multi Drug Resistant (MDR) Bacteria through duodenoscopes. The aim of this survey was to evaluate the current clinical practice of management of ERCP associated infections in Emilia-Romagna, Italy. Methods: An online survey was developed including 12 questions on management of ERCP associated infections risk. The survey was proposed to all 12 endoscopy centers in Emilia Romagna that perform at least > 200 ERCPs per year. Results: 11 centers completed the survey (92%). Among all risk factors of ERCP infections, hospitalization in intensive care units, immunosuppressant therapies, and previous MDR infections have achieved a 80 % minimum of concurrence by our respondents. The majority of them did not have a formalized document in their hospital describing categories and risk factors helpful in the detection of patients undergoing ERCP with an high-level infective risk (9/11, 82%). Most centers (8/11, 72%) do not perform screening in patients at risk of ERCP infections. Post procedural monitoring is performed by 6 of 11 centers (55%). Conclusion: Our survey showed that, at least at regional level, there is a lack of procedures and protocols related to the management of patients at risk of ERCP infections.

Endoscopic submucosal dissection for superficial premalignant and malignant epithelial neoplasms of the digestive tract: a real-life experience in Italy.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is a technique for en bloc resection of neoplastic lesions of the digestive tract. Endoscopic submucosal dissection was developed in Asia, and data from Western countries are scarce. Our study aimed to assess the efficacy and safety of ESD for resection of superficial premalignant and malignant epithelial neoplasms in a tertiary center in Italy. PATIENTS AND METHODS: All patients with gastrointestinal lesions who underwent ESD between January 2013 and December 2018 in our center were retrospectively evaluated. Technical success, en bloc, R0, curative resection, and complication rates were assessed. RESULTS: A total of 107 lesions (stomach, no.=41; rectum, no.=32; colon, no.=28; esophagus, no.=5; duodenum, no.=1) were resected by ESD in 93 patients. Endoscopic submucosal dissection was technically successful in 99.1% (106/107) of lesions. Among the 90 superficial premalignant and malignant epithelial neoplasms, en bloc, and R0 resection rates were 97.8% (no.=88) and 75.6% (no.=68), respectively. Major complications occurred in 9.3% (10/107) of cases: 4 (3.7%) were perforations and 6 (5.6%) were major bleedings. All complications, but two which needed surgery, were managed endoscopically. CONCLUSIONS: Our study shows that ESD is a feasible, effective, and safe technique in a Western country.

Role of Formyl Peptide Receptors in Gastrointestinal Healing.

The wound healing and the barrier restoration of the gastrointestinal (GI) mucosa must be continuously ensured to allow homeostasis of the gastrointestinal tract and of all the surrounding tissues. Several lines of the evidence report a key role of innate immunity, and in particular of Pattern Recognition Receptors (PRRs), in controlling the homeostasis of GI tract by sensing commensal and pathogen bacteria, activating the immune response and regulating epithelial repair, thus guaranteeing the morphological and functional recovery of the injured tissue. We will discuss the role of a particular class of PRRs - the Formyl Peptide Receptors - in the homeostasis of GI mucosa. We here report the results of studies that strongly suggest the possibility that the activation of FPRs is crucial in the maintenance of homeostasis of the GI tract and provide indications of the potential clinical relevance of new treatment regimens involving FPR modulation for several GI disorders.

Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis.

BACKGROUND: The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test is still uncertain. AIM: To assess the diagnostic performance of the serum panel test for the diagnosis of atrophic gastritis. METHODS: Medline via PubMed, Embase, Scopus, Cochrane Library databases and abstracts of international conferences proceedings were searched from January 1995 to December 2016 using the primary keywords "pepsinogens," "gastrin," "atrophic gastritis," "gastric precancerous lesions." Studies were included if they assessed the accuracy of the serum panel test for the diagnosis of atrophic gastritis using histology according to the updated Sydney System as reference standard. RESULTS: Twenty studies with a total of 4241 subjects assessed the performance of serum panel test for the diagnosis of atrophic gastritis regardless of the site in the stomach. The summary sensitivity was 74.7% (95% confidence interval (CI), 62.0-84.3) and the specificity was 95.6% (95%CI, 92.6-97.4). With a prevalence of atrophic gastritis of 27% (median prevalence across the studies), the negative predictive value was 91%. Few studies with small sample size assessed the performance of the test in detecting the site of atrophic gastritis. CONCLUSIONS: The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis. This test may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis; however, a cost-effectiveness analysis is needed.

Can early precut implementation reduce endoscopic retrograde cholangiopancreatography-related complication risk? Meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: Precut papillotomy is considered a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)-related complications; however whether the complication risk is due to precut itself or to the prior prolonged attempts is still debated; therefore, early precut implementation has been suggested to reduce the complication rate. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing cannulation and complication rates of early precut implementation with persistent attempts by the standard approach. METHODS: RCTs that compared cannulation and complication rates of the early precut implementation and of persistent attempts by the standard approach were included. Summary effect sizes were estimated by odds ratio (OR) with a random-effects model and by Peto OR. RESULTS: Six RCTs with a total of 966 subjects met the inclusion criteria. Overall cannulation rates were 90 % in both randomization groups (OR 1.20; 95 % confidence interval [CI] 0.54 - 2.69). Post-ERCP pancreatitis developed in 2.5 % of patients randomized to the early precut groups and in 5.3 % of patients from the persistent attempts groups (OR 0.47; 95 %CI 0.24 - 0.91). The overall complication rates, considering pancreatitis, bleeding, cholangitis, and perforation rates, were 5.0 % in the early precut groups and 6.3 % in the persistent attempts groups (OR 0.78; 95 %CI 0.44 - 1.37). CONCLUSIONS: RCTs that investigated the issue of timing of the precut procedure were limited. Current evidence suggests that in experienced hands the early implementation of precut and persistent cannulation attempts have similar overall cannulation rates; early precut implementation reduces post-ERCP pancreatitis risk but not the overall complication rate. Further studies are needed to confirm these findings.

Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia-related bleeding in patients with liver cirrhosis.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is a cause of bleeding in patients with liver cirrhosis. Argon plasma coagulation (APC) is the most used endoscopic treatment for GAVE-related bleeding. Treatment failures have been described in patients with haemorrhagic diathesis; post-procedure complications include haemorrhages and septicaemia. The aim of the study was to evaluate efficacy and safety of APC treatment of GAVE-related bleeding in patients with liver cirrhosis. METHODS: Patients included were suffering from GAVE-related bleeding and liver cirrhosis. APC treatment was performed until eradication. Resolution of transfusion-dependent anaemia and evaluation of complications were the primary outcomes. RESULTS: 20 patients (16 Child C and 4 Child B) were enrolled and prospectively followed for a mean period of 28 months. GAVE eradication was achieved in all patients after a median of 3 sessions (range 1-10). Resolution of anaemia was achieved in 18 patients. Six patients had relapse of GAVE after a mean of 7.7 months, successfully retreated by APC. Hyperplastic polyps developed in 3 patients causing active bleeding in 2 cases. Five patients had liver transplants and 1 had a relapse of GAVE after transplantation. CONCLUSION: APC is an effective and safe endoscopic treatment for GAVE in patients with liver cirrhosis.

Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study.

OBJECTIVE: Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. METHODS: 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). RESULTS: The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett's oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett's oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett's oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. CONCLUSIONS: GORD is common in Italy, but the prevalence of Barrett's oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett's oesophagus often have no reflux symptoms.

Systematic review: Helicobacter pylori eradication for the prevention of gastric cancer.

BACKGROUND: Helicobacter pylori is recognized as one of the most significant risk factors for gastric cancer, and H. pylori eradication has been proposed as a possible primary chemo-preventive strategy to reduce gastric cancer incidence. AIM: To evaluate the available evidence on the efficacy of H. pylori eradication in the prevention of gastric cancer. METHODS: Epidemiological, observational and interventional studies, as well as decisional models, were taken into account in this review. RESULTS: Large-scale epidemiological studies clearly link H. pylori infection with non-cardia gastric cancer. Current evidence suggests that, in a subpopulation of treated subjects, H. pylori eradication prevents the progression of preneoplastic lesions. Studies that have attempted to evaluate the effect of H. pylori eradication on the incidence of gastric cancer have not provided definitive answers. H. pylori eradication seems to reduce the incidence of gastric cancer in patients without baseline precancerous gastric lesions. Decisional models suggest that H. pylori screening could be cost-effective, but there is not yet sufficient evidence to support the setting up of a general screening programme. CONCLUSION: Helicobacter pylori eradication is a plausible intervention for gastric cancer prevention; however, it seems to be relevant in only a subset of subjects.

Measuring dyspepsia: a new severity index validated in Bologna.

BACKGROUND: Measurement of the severity of dyspepsia symptoms before and after treatment and determining what is a significant change is a major problem in designing dyspepsia treatment studies. OBJECTIVES: To assess the reproducibility, validity and responsiveness to treatment of a dyspepsia questionnaire to be used in clinical and population-based studies. METHODS: Seventy-three dyspeptic patients (35 male, 38 female; mean age 52 years) and 75 healthy volunteers (32 male, 43 female; mean age 52 years) were included. Subjects were interviewed for the presence/absence and severity/frequency of 19 gastrointestinal symptoms. Severity was measured on a 5-point scale. Frequency was also recorded on a 5-point scale. A global symptom index (severity x frequency) was calculated for the eight most severe symptoms; a mean global symptom index (8-MGSI) was considered for the evaluation of the instrument. To evaluate intra-observer variation, one author interviewed subjects (T0) and then repeated the interview 1 week later (T1). For inter-observer variation, two authors interviewed patients. VALIDITY was measured by comparing 8-MGSI of the dyspepsia patients to those of healthy volunteers. Responsiveness was assessed by comparing mean global symptom index before and 1 month after appropriate therapy. RESULTS: Reproducibility: The mean 8-MGSI was 4.5 at T0 and 3.7 at T1 with a correlation coefficient of 0.62. As for inter-observer variation, the average 8-MGSI was 4.8 by the first author and 3.9 by the second with a correlation coefficient of 0.60. VALIDITY: The mean 8-MGSI was, respectively, 1.4 in healthy volunteers and 4.8 in dyspeptic patients (p = 0.001). Responsiveness: After treatment, a significant improvement in 8-MGSI was detected (p = 0.001). CONCLUSIONS: This questionnaire is a reliable, valid and responsive instrument for measuring the presence, severity and frequency of dyspepsia.

An inter- and intra-laboratory comparison of breath ¹³CO2analysis.

BACKGROUND: ¹³C breath test analysis requires accurate ¹³CO2measurements. AIM: To perform a multicentre study to evaluate the repeatability and reproducibility of breath ¹³CO2analysis. METHODS: Two series of 25 paired randomly coded tubes (each consisting of 23 ¹³CO2-enriched breath samples and two samples of standard reference pure CO2with certified δ ¹³C(PDB)) were sent to participating centres for ¹³CO2measurement. Each series of tubes was analysed 10 days apart. The repeatability and reproducibility of ¹³C measurements was assessed by Mandel's k and h statistics. RESULTS: Twenty-two centres participated in the study: 18 showed good inter- and intra-laboratory variability, whilst four showed abnormally high inter- or intra-laboratory variability. Breath test results were also significantly affected by the accuracy of the ¹³C analytical procedures. CONCLUSIONS: A low accuracy of ¹³C measurements may significantly affect the results of breath tests, leading to inappropriate clinical decisions. Standardization of ¹³C analysis is required to guarantee optimal ¹³C measurements and accurate ¹³C breath test results.

Helicobacter pylori and functional dyspepsia: review of previous studies and commentary on new data.

Many studies have attempted to prove a link between Helicobacter pylori infection and functional dyspepsia but the results have been conflicting. Several mechanisms have been postulated for how H pylori associated inflammation disturbs antral and duodenal function but no pathophysiological explanation of how H pylori may cause dyspeptic symptoms is presently available.

Treatment of Helicobacter pylori infection. Indications and regimens: an update.

The management of Helicobacter pylori infection is still surrounded by controversy and uncertainties. Indications and correct application of current regimens for Helicobacter pylori infection are still considered a matter of debate. Regarding indications, only peptic ulcer and mucosa associated lymphoid tissue lymphoma are considered clear indications for treatment. In other conditions, such as atrophic gastritis, post gastric cancer resection, first-degree relatives of gastric cancer patients, dyspeptic patients, patients with gastro-oesophageal reflux disease and non-steroidal anti-inflammatory drug users, the value of Helicobacter pylori eradication is still controversial. The regimens for first-line and second-line treatment of Helicobacter pylori infection have been recommended by the Maastricht 2 Consensus Report. Although all the treatments are considered to be effective, physicians still do not agree on what first-line regimen should be used. Furthermore, a consensus on the duration of the antibiotic treatment is still lacking, although Maastricht guidelines for treatment of Helicobacter pylori infection recommend a one-week therapy. Also regimens, as a third-line treatment, and methods to improve compliance and clinical outcome are still a matter of debate. All these points will be considered in the present review

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection.

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.

Endoscopic surveillance in Barrett's esophagus.

Barrett's esophagus (BE), a complication of chronic gastroesophageal reflux disease (GORD), is a condition that is premalignant for adenocarcinoma of the esophagus and esophagogastric junction. Esophageal adenocarcinoma, once an uncommon entity, has been growing rapidly in incidence over the last two decades in several parts of the world. Barrett's esophagus is a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy (American College of Gastroenterology guidelines). Because of its premalignant nature, it is recommended that patients with BE undergo regular endoscopic surveillance. The recommendation for endoscopic surveillance is based on unproved and controversial assumptions including: 1) the assumption that Barrett's esophagus adversely influences survival; 2) the assumption that endoscopic surveillance can reliably detect early, curable neoplasia in the columnar lined esophagus. Moreover, the low incidence of adenocarcinoma (reported cancer incidence rates in prospective studies on BE range between 0.5% and 1.9%) is used to support an approach of not surveying patients with Barrett's esophagus. Despite these not convincing data, endoscopic surveillance is considered ''reasonable'' and ''desirable'' by the gastroenterological associations and consensus meetings. Endoscopic surveillance for cancer in Barrett's esophagus (BE) is performed primarily to seek dysplasia, to prevent the progression to invasive malignancy; however, one of the limitations of using dysplasia is a lack of understanding of its natural history. The efficacy of endoscopic surveillance for Barrett's esophagus is likely to remain unclear for a long time. The American College of Gastroenterology has recommended the following practice guidelines: a) for patients with no dysplasia, surveillance endoscopy is recommended at an interval of every 2 to 3 years; b) for patients with low grade dysplasia, surveillance endoscopy every 6 months for the first year is recommended, followed by yearly endoscopy if the dysplasia has not progressed in severity; c) for patients with high grade dysplasia, two alternatives are proposed after the diagnosis has been confirmed by an expert gastrointestinal pathologist. One alternative is intensive endoscopic surveillance until intramucosal cancer is detected at an interval of every 3-6 months. The other alternative is esophageal resection. In the situation of indeterminate dysplasia, whereas the pathologist can not come to definite diagnosis, control biopsies are proposed after 2 months of adequate acid suppression by means of proton pump inhibition. In all cases, the technique of random, four quadrant biopsies taken every 2 cm in the columnar-lined esophagus for standard histologic evaluation is recommended. Any grossly abnormal areas may be biopsied too. One can expect however that during the next future these protocol will change considering new data on dysplasia detection (biochemical markers, flow cytometry), new techniques to identify dysplasia (chromoendoscopy, endosonography, coherence optical tomography, fluorescence techniques) and development of better ablative techniques. At present a marker other than dysplasia identifying a high risk group for cancer on which to focus endoscopic surveillance has not yet been established.

The Loiano-Monghidoro population-based study of Helicobacter pylori infection: prevalence by 13C-urea breath test and associated factors.

OBJECTIVES: As part of a cross-sectional study on cholelithiasis, 1533 out of 1840 residents in Loiano/Monghidoro, a rural area in Northern Italy (792 men, 741 women, age range 28-80 years), agreed to be further evaluated in relation to their Helicobacter pylori status. METHODS: Each participant performed a 13C-urea breath test (13C-UBT) and provided information on sociodemographic, lifestyle and clinical characteristics. RESULTS: The 13C-UBT was positive in 1041 subjects (67.9%; men: 69%; women: 67%) and was positively associated with increasing age (P < 0.001), alcohol consumption (P < 0.01), a higher number of siblings (P < 0.001) and a personal history of peptic ulcer (P < 0.01), but inversely with a nonmanual occupation (P < 0.001). Overall, H. pylori infection was unrelated to smoking, house pets, and a family history of gastroduodenal diseases. The prevalence of H. pylori infection was 72% in subjects reporting one or more dyspeptic symptoms and 65% among asymptomatic participants (P < 0.001); a multivariate analysis showed that only epigastric pain was significantly, although weakly, associated with 13C-UBT positivity. CONCLUSIONS: This large population-based study showed a prevalence of H. pylori infection higher than that reported by serologic surveys in urban areas. Current H. pylori infection was strongly associated with indicators of lower socioeconomic status, alcohol consumption and increasing age. A role of H. pylori infection in determining epigastric pain was suggested.

Incidence and recurrence rates of colorectal adenomas in first-degree asymptomatic relatives of patients with colon cancer.

OBJECTIVES: Subjects with one first-degree relative affected with colorectal cancer are considered to be at increased risk of colorectal adenomas. We compared the recurrence and incidence rates of colorectal adenomas among subjects with one first-degree relative with colorectal cancer and those without family history. METHODS: A series of consecutive asymptomatic subjects successfully underwent a colonoscopy, were found to have either normal results or at least one adenoma, provided a detailed family history, and were offered a second colonoscopy 3 yr later; 190 out of 436 subjects accepted, 134/172 with one or more adenomas and 56/264 with no abnormalities at the initial examination. A first-degree family history was reported by 43/134 and 26/56, respectively. RESULTS: By multivariate analysis, the presence of adenomas at follow-up examination was significantly associated with a positive family history of colorectal cancer in both subgroups, those with a previously resected adenoma (odds ratio = 2.23, 95% CI = 1.04-4.79) and those without (odds ratio = 8.95, CI = 1.29-62.22). CONCLUSION: A history of one first-degree relative with colorectal cancer is associated with a significant increase in 3-yr cumulative incidence and recurrence rates of adenomas.