Spyros Potamianos

Laparoendoscopic rendezvous versus preoperative ERCP and laparoscopic cholecystectomy for the management of cholecysto-choledocholithiasis: interim analysis of a controlled randomized trial.

Background:Although the ideal management of cholecysto-choledocholi-thiasis is controversial, the 2-stage approach [endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, and common bile duct (CBD) clearance followed by laparoscopic cholecystectomy] remains the standard way of management worldwide. One-stage approach using the so-called laparoendoscopic rendezvous (LERV) technique offers some advantages, mainly by reducing the hospital stay and the risk of post-ERCP pancreatitis. Objective:To compare the LERV 1-stage approach with the standard 2-stage approach consisting of preoperative ERCP followed by laparoscopic cholecystectomy for the treatment of cholecysto-choledocholithiasis. Setting:Controlled randomized trial, University/Teaching Hospital. Methods:Patients with cholecysto-choledocholithiasis were randomized either to LERV or to the 2-stage approach. Both elective and emergency cases were included in the study. Primary endpoint was to detect difference in overall hospital stay, whereas secondary endpoints were (i) to detect differences in morbidity (especially post-ERCP pancreatitis) and (ii) success of CBD clearance. This is an interim analysis of the first 100 randomized patients. Results:Hospital stay was significantly shorter in the LERV group; median 4 (2–19) days versus 5.5 (3–22) days, P = 0.0004. There was no difference in morbidity and success of CBD clearance between the 2 groups. Post-ERCP amylase value was found significantly lower in the LERV group: median 65 (16–1159) versus 91 (30–1846), P = 0.02. Conclusions:Interim analysis of the results suggests the superiority of the LERV technique in terms of hospital stay and post-ERCP hyperamylasemia.

Calprotectin, Calgranulin C, and Other Members of the S100 Protein Family in Inflammatory Bowel Disease

BackgroundSince their discovery, S100 proteins have been associated with diverse diseases of inflammatory, degenerative, or malignant nature. Due to their participation in inflammation, they have also been studied with regard to inflammatory bowel disease (IBD).MethodTo provide a review of available literature, a PubMed, MEDLINE, and Embase-based literature search was performed, using all available nomenclature for each member of the S100 protein family, along with the terms inflammatory bowel disease, ulcerative colitis, Crohn’s disease, or indeterminate colitis.ResultS100A8/A9, also known as calprotectin, S100A12, or calgranulin C and in a lesser extent S100P, are involved in the pathogenesis, activity, diagnosis, and therapeutic management of IBD. The majority of available literature is focused primarily on S100A8/9, although there is growing evidence on the significance of S100A12. Most studies emphasize the potential merit of S100A8/A9 and S100A12, as markers for differential diagnosis, monitoring of activity, or disease relapse, in IBD. Limitations, regarding the diagnostic utility of these markers, seem to exist and are mainly related to the publication of conflicting results, i.e., for IBD activity, and to the fact that S100A8/A9 and S100A12 are not disease-specific.ConclusionsAlthough the existing data link specific S100 proteins with IBD, there are still several drawbacks in the use of these markers for diagnostic purposes. Thus, it seems that further research is mandatory in order to eliminate the impact of confounding factors but also to detect additional associations between S100 proteins and IBD or novel S100 proteins with a closer correlation with IBD.

TLR4 gene polymorphisms: evidence for protection against type 2 diabetes but not for diabetes-associated ischaemic heart disease

OBJECTIVE Several factors either predisposing or protecting from the onset of diabetes mellitus type 2 (DM2) have been proposed. Two specific polymorphisms of toll-like receptor 4 (TLR4; Asp299Gly and Thr399Ile) have recently been identified either as candidate protector genes against DM2 and associated neuropathy or risk alleles for the manifestation of diabetic retinopathy. The impact of these alleles on the risk for ischaemic heart disease (IHD) is controversial while their role in diabetes-associated IHD has never been studied. DESIGN AND METHODS In order to clarify the potential impact of TLR4 polymorphisms on the predisposition for DM2 as well as on diabetes-related IHD vulnerability, the distribution of the mutant TLR4 Asp299Gly and Thr399Ile alleles in 286 DM2 patients and 413 non-DM2 controls with or without IHD, was examined. RESULTS Mutant alleles were predominantly detected in 79/413 non-diabetic individuals versus 15/286 DM2 patients (P<0.0001). The rates of positivity for mutant alleles were similar among diabetic patients with or without IHD (7/142 vs 8/144, P>0.1), whereas they proved different among non-diabetic individuals with or without IHD (39/145 vs 40/268, P=0.004). Following multivariate analysis, the difference between diabetic and non-diabetic subjects, with regard to TLR4 mutations alone, remained significant (P=0.04). CONCLUSIONS Mutant TLR4 alleles confer protection against DM2. However, their presence does not seem to play any role, protective or aggravating, in the manifestation of IHD either in diabetic or in non-diabetic individuals.

Prevalence and clinical significance of immunoglobulin A antibodies against tissue transglutaminase in patients with diverse chronic liver diseases.

ABSTRACT The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microsphere-based flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb+ EmA+ and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs+ EmA+ (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs+ EmA− (5.8%; P < 0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P = 0.008), cirrhosis (P = 0.004), alkaline phosphatase (P = 0.026), and antinuclear antibodies (P = 0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.

Habib EndoHPB: A Novel Endobiliary Radiofrequency Ablation Device. An Experimental Study

ABSTRACT Background: The Habib EndoHPB is a bipolar radiofrequency (RF) catheter developed to be introduced across malignant strictures of the bile ducts, so that RF energy can locally ablate the tumor prior to stent placement. This experiment aims to assess the ability of the catheter to coagulate the wall of the common bile duct (CBD) in a porcine model, to establish power requirement and time parameters and correlate them to the depth of thermal injury, and to assess the ease of operation of the device. Methods: The CBD was catheterized using the device in 20 pigs. RF energy was applied to the CBD wall with various generator settings. The pigs were sacrificed 24 hr after the application and the CBD was excised for histological analysis. Results: The device was easy to handle. Statistically significant correlations between the power, the time of RF application, and the thermal injury depth were found. Conclusion: The Habib EndoHPB catheter can effectively deliver RF energy intraluminally in the porcine CBD. Clinical studies are warranted in order to define proper settings for safe and efficient use in malignant biliary obstruction.

High-Dose Pantoprazole Continuous Infusion Is Superior to Somatostatin After Endoscopic Hemostasis in Patients With Peptic Ulcer Bleeding

BACKGROUND:The best antisecretory treatment after endoscopic hemostasis in patients with ulcer bleeding is still in quest.OBJECTIVES:To compare pantoprazole and somatostatin continuous infusion after endoscopic hemostasis in patients with bleeding peptic ulcers.PATIENTS AND METHODS:A total of 164 consecutive patients with a bleeding peptic ulcer, after successful endoscopic hemostasis, were randomly assigned to receive, double blindly, continuous IV infusion of pantoprazole 8 mg/h for 48 h after a bolus of 40 mg (group P) or somatostatin 250 μg/h for 48 h after a bolus of 250 μg (group-S). Twenty-four-hour pH-metry was performed in the last 30 patients in each group. Endoscopy was performed, in case of bleeding nonrecurrence, every 48 h until disappearance of stigmata.RESULTS:Bleeding recurrence: group S 14 patients (17%) versus group P 4 (5%) (P = 0.046). In multivariate analysis, bleeding recurrence was 4.57 (CI 1.31–15.91) times more frequent in group S (P = 0.02). There was no difference in the need for surgery and mortality. Acid suppression over pH 6: group S 82.9% of the time versus group P 81.5% (P = 0.97). Acid suppression over pH 6 for >85% of the time: group S 14 (47%) patients versus group P 17 (57%) (P = 0.44). Disappearance of endoscopic stigmata after 48 h: group S 25/68 patients (37%) versus group P 72/78 (92%) (P < 0.0001). No major side effects identified in either study group.CONCLUSIONS:In patients with a bleeding ulcer, after successful endoscopic hemostasis, despite equipotent acid suppression, pantoprazole continuous infusion was superior to somatostatin to prevent bleeding recurrence and quick disappearance of the endoscopic stigmata. Nevertheless, no differences were seen in the need for surgery and mortality.

Prevalence of coeliac disease in the adult population of central Greece.

Objectives Recent studies from several countries have shown that coeliac disease (CD) is increasingly being diagnosed in adults, as the availability of new, accurate serologic tests has made screening in the general population possible. No data exist regarding the prevalence of CD in Greece. The aim of this study was the implementation of a serologic screening procedure for CD in the adult general population of Thessaly, an area of central Greece, using a novel diagnostic algorithm. Methods The study included 2230 participants (1226 women, 1004 men, median age 46 years, range 18–80 years), selected by systematic random sampling, from the adult general population of Thessaly. All the serum samples were tested for total immunoglobulin A (IgA)-serum levels, to exclude IgA deficiency. Samples with total IgA within the normal range were tested for IgA antibodies against native human-tissue transglutaminase (anti-tTG); samples that were anti-tTG positive were tested for IgA antiendomysial antibodies (EmA). Samples from participants with selective IgA deficiency were examined for IgG antigliadin antibodies. Participants who were EmA-positive or antigliadin antibody-positive were referred for intestinal biopsy and human leucocyte antigen (HLA) typing. Results No participant with selective IgA deficiency was detected. Four individuals tested positive for EmA, all of whom were biopsy-proven coeliacs. Therefore, the CD prevalence in this general population sample is 1 : 558 or 1.8 per 1000 (SE 0.13). The four new patients with abnormal histology (two men, two women) were aged between 18 and 35 years. Two of them were considered to be asymptomatic and two presented with a subclinical course. All four had the heterodimer HLA-DQ2. Conclusions This first serological screening study for CD in Greece has demonstrated that CD prevalence in Thessaly is among the lowest reported in Europe.

The implication of adiponectin and resistin in gastrointestinal diseases

Adiponectin and resistin, members of the adipokine family, are multi-task hormones involved in several disorders, including those of the alimentary tract. In the present review, eligible studies focusing on the role of adiponectin and resistin in gastrointestinal diseases are manifested together and classified according to anatomic criteria. In addition, similarities and common patterns have been recognized, ultimately revealing an inverse association: the down-regulation of adiponectin and up-regulation of resistin - both in vitro and in vivo - in gastrointestinal disorders, irrespective of their diverse nature - inflammatory, autoimmune or malignant - or anatomic position - esophageal, gastric, of the small intestine, colonic. Finally, a potential role for both adipokines in alimentary tract-related carcinogenesis has been identified, possibly representing a missing link between obesity and cancer.

Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels, in patients with inflammatory bowel disease

BackgroundTissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).MethodsTIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohns disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded.ResultsMean serum TIMP-1 levels were 414.9 ± 17.6 ng/mL in UC patients, 446.1 ± 22.8 ng/mL in CD patients and 296.5 ± 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p < 0.0001 in both groups). Mean serum TIMP-1 levels were significantly higher in patients with active IBD (450.5 ng/mL) in comparison with patients with inactive disease (417.3 ng/mL, p = 0.03). Moreover, males showed significantly higher mean serum TIMP-1 levels (399.8 ng/mL), compared to females (368.5 ng/mL, p = 0.04). Mean serum TIMP-2 levels did not differ between UC and CD patients or HC (p > 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 ± 67.7 pg/mL in UC patients, 1708.1 ± 73.4 pg/mL in CD patients and 5573.4 ± 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03).ConclusionAn imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter.

Increased fetuin A levels in Helicobacter pylori infection: a missing link between H. pylori and insulin resistance?

To the Editor: Helicobacter pylori infection has been associated with diverse biological processes, including inflammation, metabolism, oncogenic transformation [1, 2]. In view of its effect on metabolic variables, H. pylori has been linked with both dyslipidaemia and insulin resistance (IR) [1, 2]. Among the various factors capable of inducing IR, the upregulation of α2-Heremans Schmid glycoprotein, also known as human fetuin A, has been linked with impaired insulin sensitivity, glucose metabolism and, subsequently, the onset of diabetes mellitus [3, 4]. Interestingly, certain pathogens have been shown to induce an increase in the level of fetuin A or fetuin A-like molecules such as Mycobacterium bovis in cattle and severe acute respiratory syndrome-coronavirus (SARSCoV) in humans [5]. Based on these data, we performed a study to investigate whether the H. pylori-induced IR is mediated through an upregulation of fetuin A levels. Determination of circulating fetuin A (by ELISA; BioSource Europe, Nivelles, Belgium), fasting insulin (by ELISA; DRG Instruments, Marburg, Germany) and glucose levels (hexokinase method, cat. no. OSR6521; Olympus Life Science Research Europa, Hamburg, Germany) was performed for 105 non-diabetic individuals (Table 1) undergoing oesophagogastroduodenoscopy owing to dyspeptic complaints. According to the results of a Campylobacter-like organism test and histology, study participants were classified into H. pylori-positive (Hp, n=72) and negative (Hp, n=33) groups matched for age, sex, BMI and smoking. For IR, the HOMA-IR (www.hepcnomads. co.uk/HOMACalc.htm, accessed 11 November 2010) was used. Details of lipoprotein, triacylglycerol and C-reactive protein (CRP) levels were also available from routine examinations. None of the participants was receiving any medication and none had any factor that could affect H. pylori diagnosis, fetuin A levels or glucose metabolism (family history of diabetes mellitus, obesity, proton pump inhibitor use, liver, kidney, systemic disorders, polycystic ovary disease). The study had been approved by the Ethics Committee of the University of Thessaly Medical School. Informed consent was obtained from all individuals prior to inclusion in the study. A. C. Manolakis : E. K. Tiaka :A. N. Kapsoritakis : F. Tsiopoulos : S. P. Potamianos (*) Department of Gastroenterology, University of Thessaly, School of Medicine, Mezourlo, 41110 Larissa, Greece e-mail: spotam@med.uth.gr