A multicenter survey on endoscopic retrograde cholangiopancreatography during the COVID-19 pandemic in northern and central Italy.

Background and study aims COVID-19 has dramatically impacted endoscopy practice because upper endoscopy procedures can be aerosol-generating. Most elective procedures have been rescheduled. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in emergency or urgent settings in which rescheduling is not possible. We evaluated the impact of the COVID-19 pandemic on ERCP in Italy during the SARS-CoV-2 lockdown, in areas with high incidence of COVID-19. Patients and methods We performed a retrospective survey of centers performing ERCP in high COVID-19 prevalence areas in Italy to collect information regarding clinical data from patients undergoing ERCP, staff, case-volume and organization of endoscopy units from March 8, 2020 to April 30, 2020. Results We collected data from 31 centers and 804 patients. All centers adopted a triage and/or screening protocol for SARS-CoV-2 and performed follow-up of patients 2 weeks after the procedure. ERCP case-volume was reduced by 44.1 % compared to the respective 2019 timeframe. Of the 804 patients undergoing ERCP, 22 (2.7 %) were positive for COVID-19. Adverse events occurred at a similar rate to previously published data. Of the patients, endoscopists, and nurses, 1.6 %, 11.7 %, and 4.9 %, respectively, tested positive for SARS-CoV-2 at follow up. Only 38.7 % of centers had access to a negative-pressure room for ERCP. Conclusion The case-volume reduction for ERCP during lockdown was lower than for other gastrointestinal endoscopy procedures. No definitive conclusions can be drawn about the percentage of SARS-CoV-2-positive patients and healthcare workers observed after ERCP. Appropriate triage and screening of patients and adherence to society recommendations are paramount.

Functional polymorphisms of the receptor for the advanced glycation end product promoter gene in inflammatory bowel disease: a case-control study.

The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.

The Circulating Level of Soluble Receptor for Advanced Glycation End Products Displays Different Patterns in Ulcerative Colitis and Crohn's Disease: A Cross-Sectional Study.

BACKGROUND: RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity. METHODS: We enrolled 60 CD, 67 UC patients, and 66 controls (all adults). Disease activity was scored through the clinical, endoscopic, and histologic indexes of severity, whilst disease location and behaviour were assessed according to the Montreal classification. In all cases, the levels of serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured. RESULTS: sRAGE levels were significantly lower in UC, both active and inactive, than in controls and CD (817.35, range 437.3-1449; 1211, range 843.7-1618; 1207.5, range 743.15-1875.75; P < 0.05 for both), and inversely correlated with clinical and endoscopic indexes of activity in both IBD groups (P < 0.05 for all) and with the histologic score in the CD group. Moreover, those CD patients with a penetrating behaviour showed a significant reduction in both sRAGE (P = 0.006) and S100A12 (P = 0.034) as compared to those with an inflammatory/stricturing pattern. Although S100A12 levels were not found up-regulated, a negative correlation appeared evident with the clinical (r = -0.38) and endoscopic (r = -0.32) indexes of activity in UC and CD, respectively. CONCLUSION: These data suggest a different role for RAGE in CD and UC, and a potential use of sRAGE as a new biomarker.

Role of the advanced glycation end products receptor in Crohn's disease inflammation.

AIM: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). METHODS: Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS: In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. CONCLUSION: RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.

Validation of the Italian translation of the Inflammatory Bowel Disease Questionnaire.

BACKGROUND: Health-related quality of life is an important measure of treatment outcome; its evaluation requires the use of internationally validated ad hoc questionnaires. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is the most used specific instrument. AIM: To assess the validity and reliability of the Italian translation of the IBDQ. METHODS: The IBDQ underwent forward and backward translation; 13 patients were enrolled for cognitive testing of the Italian version to increase clarity. For field testing, 113 patients (65 with Crohn's disease and 48 with ulcerative colitis) completed both the IBDQ and the generic instrument 36-item Short Form Health Survey scale (SF-36). RESULTS: Data quality was optimal with high completeness and low floor and ceiling effect. Item internal consistency was satisfied for 100% of patients, while discriminant validity showed a few items with higher correlations with other scales. Cronbach's alpha coefficient was 0.96. Test-retest correlations indicated good reliability (Pearson R 0.81). Exploratory factor analysis indicated that the original grouping of the item was suboptimal. The score proved sensitive to disease activity, gender and quality of life as measured by the SF-36. CONCLUSIONS: The Italian translation of the McMaster Inflammatory Bowel Disease Questionnaire sounds natural and is easy to understand. A field test gave results comparable to other international validations, supporting its use in cross-national surveys.

Use of double-balloon enteroscopy in the management of patients with Crohn's disease: feasibility and diagnostic yield in a high-volume centre for inflammatory bowel disease.

BACKGROUND: Double-balloon enteroscopy (DBE) is theoretically useful in Crohn's disease (CD) since it is potentially able to investigate the whole small intestine, but sparse data are available. AIM: To assess the feasibility, safety, and diagnostic yield of DBE in CD. METHODS: The study was conducted in a tertiary care centre for inflammatory bowel disease. Thirty-seven patients with CD (18/19 male/female, mean age 42 years, range 13-77 years) were considered. Thirty-two DBEs from the oral approach and 18 from the anal (in 6 patients from both ways with a complete exploration in 4, 10.8%) were performed. Indications were: first diagnosis/staging in 16 cases, diagnosis of stenosis in 7, obscure bleeding in 10, suspected neoplasia in 2, and postsurgical evaluation in 2. One hundred and thirty-three other procedures (3.7 per patient) were performed with the same indication. RESULTS: Insertion depth from the oral route was 266.5 ± 100 cm and from the anal route 72.5 ± 60 cm. Ileocecal valve was passed in 8/13 patients, but in 4 DBE explored less than 50 cm of ileum. Diagnostic yield was 59.4% but changed according to indication (40% in obscure bleeding, 100% in case of strictures) and was higher when DBE was conducted on the basis of previous investigations (77.8% versus 40%, p = 0.037). CONCLUSION: DBE is a feasible, useful, but technically demanding method in CD. Definition of the proper introduction route by means of previous investigations is associated with a higher efficacy of DBE.

Appropriateness and diagnostic yield of colonoscopy in the management of patients with ulcerative colitis: a prospective study in an open access endoscopy service.

BACKGROUND: Colonoscopy is frequently performed in ulcerative colitis (UC), but its benefit in the management of the disease is a matter of debate. The objective was to determine the clinical impact of colonoscopy in UC. METHODS: Consecutive patients with UC undergoing colonoscopy were studied. The design and main outcome measurement was appropriateness of indications, evaluated according to guidelines. Endoscopic findings altering the management of the patients were registered. The endoscopist's management decisions based on patient's clinical picture were compared with those selected after endoscopy. Need for further investigations was recorded. Endpoints for colonoscopy-improving management were prospectively defined: change in medical therapy, need for adjunctive procedures, identification or exclusion of cancer, adenomatous polyps, or other conditions with clinical impact. The setting was an open access endoscopy service in a tertiary care center. RESULTS: In all, 507 patients (268 male, 239 female, mean age 42 years) were included. Colonoscopy was indicated in 60.8% of cases. In 46% of patients endoscopy revealed a significant lesion; this rate was higher for indicated (67.2) than for not indicated procedures (13.5%, P < 0.0001). The endoscopist's decision was altered by the endoscopic finding in 7.6% of cases and was not different between appropriate and inappropriate procedures. CONCLUSIONS: Endoscopy is a potent tool in the management of UC if correctly used. However, in the majority of cases a correct therapeutic decision may be established simply on the basis of the clinical picture. Relevant endoscopic findings have a relatively low impact on the medical treatment, but may have a very important value in the prognostic assessment of the disease.

Outcome of non-variceal acute upper gastrointestinal bleeding in relation to the time of endoscopy and the experience of the endoscopist: a two-year survey.

AIM: To prospectively assess the impact of time of endoscopy and endoscopist's experience on the outcome of non-variceal acute upper gastrointestinal (GI) bleeding patients in a large teaching hospital. METHODS: All patients admitted for non-variceal acute upper GI bleeding for over a 2-year period were potentially eligible for this study. They were managed by a team of seven endoscopists on 24-h call whose experience was categorized into two levels (high and low) according to the number of endoscopic hemostatic procedures undertaken before the study. Endoscopic treatment was standardized according to Forrest classification of lesions as well as the subsequent medical therapy. Time of endoscopy was subdivided into two time periods: routine (8 a.m.-5 p.m.) and on-call (5 p.m.-8 a.m.). For each category of experience and time periods rebleeding rate, transfusion requirement, need for surgery, length of hospital stay and mortality we compared. Multivariate analysis was used to discriminate the impact of different variables on the outcomes that were considered. RESULTS: Study population consisted of 272 patients (mean age 67.3 years) with endoscopic stigmata of hemorrhage. The patients were equally distributed among the endoscopists, whereas only 19% of procedures were done out of working hours. Rockall score and Forrest classification at admission did not differ between time periods and degree of experience. Univariate analysis showed that higher endoscopist's experience was associated with significant reduction in rebleeding rate (14% vs 37%), transfusion requirements (1.8+/-0.6 vs 3.0+/-1.7 units) as well as surgery (4% vs 10%), but not associated with the length of hospital stay nor mortality. By contrast, outcomes did not significantly differ between the two time periods of endoscopy. On multivariate analysis, endoscopist's experience was independently associated with rebleeding rate and transfusion requirements. Odds ratios for low experienced endoscopist were 4.47 for rebleeding and 6.90 for need of transfusion after the endoscopy. CONCLUSION: Endoscopist's experience is an important independent prognostic factor for non-variceal acute upper GI bleeding. Urgent endoscopy should be undertaken preferentially by a skilled endoscopist as less expert staff tends to underestimate some risk lesions with a negative influence on hemostasis.

Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.

BACKGROUND & AIMS: Because the reoperation rate for Crohn's disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn's disease. METHODS: In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg. kg -1. day -1 ) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn's Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery. RESULTS: After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47-15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04). CONCLUSIONS: While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.