Simone Bertolini

Connections between genetics and clinical data: Role of MCP-1, CFTR, and SPINK-1 in the setting of acute, acute recurrent, and chronic pancreatitis.

OBJECTIVES:Acute, acute recurrent, and chronic pancreatitis are inflammatory diseases with multifactorial pathogenic mechanisms. Genetic mutations and polymorphisms have been correlated with pancreatitis. The aim of this study was to investigate the association of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) gene mutations and monocyte chemoattractant protein 1 (MCP-1) –2518A/G polymorphism with acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP), and to associate genetic backgrounds with clinical phenotype in these three conditions.METHODS:One hundred eighteen AP, 64 ARP, 142 CP patients, and 88 normal controls were enrolled consecutively. We analyzed MCP-1 serum levels using enzyme-linked immunosorbent assay. Polymorphism −2518 of MCP-1 and SPINK-1 N34S gene mutations were determined by PCR–restriction-fragment length polymorphism. Sequence analysis was performed when necessary. Thirty-three CFTR mutations were analyzed in CP and ARP patients using multiplex DNA testing.RESULTS:Serum MCP-1 levels were significantly higher in all patients affected by pancreatic inflammatory diseases. Moreover, we found a significant over-representation of the MCP-1G allele in ARP patients. We found a statistically significant association of CFTR gene mutations with ARP, but not with CP. We did not find a statistically significant association of ARP or CP with the N34S SPINK-1 gene mutation. Interestingly, 39 of 64 ARP patients (61%) carried at least one genetic mutation and/or polymorphism. Five of 64 ARP patients had pancreas divisum and four of these five also carried the G allele.CONCLUSIONS:Analysis of a comprehensive range of potential susceptibility variants is needed to support modeling of the effects of genes and environment in pancreatitis. As such, beyond gene mutations, the context within which those mutations exist must be considered. In pancreatitis the context includes the inflammatory response, clinical features, and exogenous factors.

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = –0.33, P < .001) and intestinal metaplasia (r = –0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

Clinical Usefulness of Serum Pepsinogen II in the Management of Helicobacter pylori Infection

Background: Serum pepsinogen II (sPGII) levels are known to increase during Helicobacter pylori infection. Aim: To assess H. pylori infection and success of H. pylori therapy by means of sPGII levels. Methods: sPGII levels were determined in 156 H. pylori-positive and 157 H. pylori-negative consecutive patients with dyspeptic symptoms. Additionally, sPGII determination was performed in 70 H. pylori-positive patients 2 months after H. pylori eradication therapy. In 29 of these 70 patients, gastroscopy was performed to evaluate the effect of H. pylori therapy on gastric activity. Results:H. pylori-positive subjects demonstrated a significantly higher mean of sPGII levels than H. pylori-negative subjects (16.8 ± 7.4 vs. 8.6 ± 3.7 µg/l; p < 0.001). The best sPGII cut-off for predicting H. pylori infection was 9.93 µg/l (sensitivity 83%, specificity 73%). The best cut-off values to evaluate success of therapy were: sPGII of 9.47 µg/l, a sPGII variation level (difference between baseline and after therapy) of 4.54 µg/l, and a sPGII Δvalue (sPGII variation divided by sPGII before therapy) of 25% (sensitivity 93%, specificity 91%). Conclusions: sPGII levels may be used as a reliable marker of H. pylori infection in the initial diagnosis as well as to evaluate H. pylori eradication and subsequent changes in gastric inflammation.

Influence of antisecretory treatment with proton pump inhibitors on serum pepsinogen I levels.

It has been reported in literature that serum pepsinogen levels rise during omeprazole and lansoprazole administration. However, the influence of pantoprazole and esomeprazole on serum pepsinogens levels is still to be assessed. The aim of this study was to evaluate the influence of proton pump inhibitor (PPI) therapy on pepsinogen I (PGI) levels. PGI and gastrin (G17) levels (EIA; Biohit, Helsinki, Finland) in 126 consecutive patients (M 57; F 69, mean age 53, range 15–91), with upper gastrointestinal symptoms at baseline condition and after 2 months of PPI treatment, were evaluated. Patients underwent a therapy schedule based on: omeprazole 20 mg b.i.d. (20 patients), pantoprazole 40 mg b.i.d. (27 patients), esomeprazole 40 mg b.i.d. (29 patients), lansoprazole 30 mg b.i.d. (21 patients) and rabeprazole 20 mg b.i.d. (26 patients) for 2 months. A significant increase in serum PGI (sPGI) levels was found after a 2‐month treatment for all five different PPIs: omeprazole, pantoprazole, esomeprazole, lansoprazole and rabeprazole (P < 0.05). The effect of rabeprazole on sPGI was less pronounced as compared with other PPIs, whereas esomeprazole achieved superior sPGI levels, with no overall statistically significant difference among the five groups (P > 0.05). However, a comparison within a single group of PPIs showed a statistical significance when the esomeprazole group was compared with the rabeprazole group (P = 0.007). sPGI levels are significantly influenced by antisecretory therapy, rising under PPI treatment. Moreover, a statistically significant difference in sPGI levels between the rabeprazole and esomeprazole groups has been demonstrated.

P.10 “GASTROPANEL TEST” IN THE CLINICAL OUTCOME OF GERD: PROSPECTIVE SIX MONTHS CLINICAL STUDY

“GASTROPANEL TEST” IN THE CLINICAL OUTCOME OF GERD: PROSPECTIVE SIX MONTHS CLINICAL STUDY L. Guida∗ ,1, P. Perazzo1 , S. Bertolini 1 , E. Morana1, D. Vaira2, C. Scarpignato1 , V. Savarino3 , L. Gatta1, L. Cavallaro4 , G. Cavestro1, M. Rugge3, A. Franze5, F. Di Mario1 1Universita di Parma, Parma; 2Universita di Bologna, Bologna; 3Universita di Padova, Padova; 4Ospedale di Belluno, Belluno; 5Ospedale Maggiore di Parma, Parma