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Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus.This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020.Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p0.001).Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

Clostridioides difficile (formerly Clostridium difficile) infection (CDI) represents a worrisome condition, often underestimated, with severe clinical presentations, frequently requiring intensive care unit (ICU) admission. The aim of the present expert statement was to give an overview of the management of CDI in critically ill patients, for whom CDI represents a redoubtable problem, in large part related to the use and abuse of antibiotics. The available knowledge about pathophysiology, risk factors, diagnosis and treatment concerning critical care patients affected by CDI has been reviewed, even though most of the existing information come from studies performed outside the ICU and the evidence on several issues in this specific context is scarce. The adoption of potential preventive and therapeutic strategies aimed to stem the phenomenon were discussed, including the faecal microbiota transplantation. This possibility could represent a highly interesting option in critically ill patients, but current evidence is limited and future well designed studies are needed. A special insight on the specific challenges that the ICU physicians may face caring for the critically ill patients with CDI was also proposed. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Helicobacter pylori (Hp) is a pathogen which causes gastric diseases from gastritis to ulcer, cancer, and MALT Lymphoma. The higher grade of virulence belongs to strains harbouring CagA oncoprotein. Hp cag Pathogenicity Island encoded Type IV Secretion System (T4SS) is supposed to form needle-like structures (pili) on Hp surface that injects cagA into the host cell cytoplasm at basolateral membrane level. Other structures such as membranous appendages have also been described on Hp surface membrane. These data were obtained from cultured cells. The aim of the present, preliminary, retrospective, study was to investigate the morphological expression of T4SS also in human gastric biopsies and revisit the morphological aspects of bacteria and host interaction.We reviewed our previous morphological findings on over 300 scanning electron micrographs of 109 gastric bioptic specimens.1) Needle-like structures (Pili) and membranous appendages have been found at the Hp gastric cell surface interface; 2) Hp polar flagella merge to apical mucous cell membrane; 3) some gastric cell microvilli became taller and projected towards bacteria; 4) in lining epithelium basal membrane holes in which bacteria penetrate are clearly visible.Hp T4SS associated structures have also been observed in human biopsies. Pili could also take nutrients from gastric mucous cells (iron); the polar flagella could anchor Hp tightly to mucous cells; the tall microvilli projected to Hp could represent defence or affinity.

We report several cases of hydrogen peroxide-related colitis that occurred in an epidemic pattern in our gastrointestinal endoscopy center during a 2-month period in early 2007. During colonoscopy using sterilized endoscopes that had been flushed with hydrogen peroxide after the peracetic acid cycle, instantaneous effervescence and blanching (the "snow white sign") were observed on the intestinal mucosa when the water button was depressed. Biopsy specimens revealed features resembling a clinical condition which used to be known as "pseudolipomatosis." At follow-up, no patient was found to have suffered morbidity associated with this peroxide colitis. Endoscopists should consider hydrogen peroxide colitis when they see a snow white sign during colonoscopy which cannot be attributed to active inflammation or organic disease of the digestive tract.

Background/Aims: Lactobacilli are used in the prevention and treatment of several diseases, but they are also known to play a role in the pathogenesis of dental caries. The aim of our study was to evaluate whether the oral administration of lactobacilli could change the salivary counts of these bacteria compared with placebo. Moreover, lactobacilli were administered in liquid and in capsule form to determine the role of direct contact with the oral cavity. Methods: Thirty-five healthy volunteers were randomized into three groups to receive lactobacilli and/or placebo for 45 days: group A (n = 14) received probiotics in capsules and placebo in liquid form; group B (n = 16) took liquid probiotics and placebo in capsules, and group C (n = 5) used placebo in both liquid and capsule form. Streptococcus mutans populations served as control. The salivary counts of lactobacilli and S. mutans were measured semi-quantitatively using the CRT® bacteria kit. Results: Compared with placebo, the oral administration of probiotics, both in capsules and in liquid form, significantly increases salivary counts of lactobacilli (p = 0.005 and p = 0.02, respectively). S. mutans populations were not significantly modified. Conclusions: The increased salivary counts of lactobacilli may indicate the need to closely monitor the dental health of patients undergoing long-term probiotics treatment, even when this treatment is administrated in a form that avoids direct contact with the oral cavity.

Summary Background: The relationship between Helicobacter pylori infection and its treatment and gastro-oesophageal reflux disease (GERD) is controversial. Aims: To establish if H. pylori infection is associated with the presence of GERD and if anti-H. pylori treatment leads to de novo GERD or rebound/exacerbation of GERD. Methods: A search of MEDLINE and EMBASE databases was made. Pooled odds ratios (OR) were calculated for de novo GERD and rebound/exacerbated GERD after anti-H. pylori therapy in case-control studies and in therapeutic trials. Results: Fourteen case-control studies and 10 clinical trials were included. Among case-control studies, pooled OR for the association between H. pylori negative status and GERD was 1.34 [95% confidence interval (CI) 1.15–1.55]. Among therapeutic trials, pooled OR for the association anti-H. pylori therapy – GERD was 2.54 (95% CI 1.92–3.37). The OR for de novo GERD was 3.25 (95% CI 2.09–5.33), and for rebound/exacerbated GERD was 2.39 (95% CI 1.75–3.34). Associations were higher among Asian studies than among North American and European studies. Conclusions: This meta-analysis shows significant association between absence of H. pylori infection and GERD symptoms, and a positive association between anti-H. pylori therapy and occurrence of both de novo and rebound/exacerbated GERD. The significance of these associations appears to have been inflated by the effect of single trials and by geographical variations.

Background: Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA) 2) to determine the relationship between ROS generation and amount of 8-OHdG. Methods: Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody. Results: 40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA(+) and 1 CagA(-)) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content. Conclusion: H. pylori infection by a CagA(+) strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.

Hepatitis C virus (HCV) has been localized in several extra-hepatic sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localization of HCV and its possible relationship with the chronic inflammatory response to Helicobacter pylori infection.Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutively enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inflammatory infiltrates (classified as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobulin heavy-chain (IgH) gene rearrangements of mucosal B cells.In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach (P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was significantly associated with marked or moderate inflammatory infiltrates. Oligoclonal IgH gene rearrangements were detected in three group A patients who harboured both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to find HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals.HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inflammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

A close relationship between elevated plasma free fatty acid (FFA) levels and insulin resistance is commonly reported in obese subjects. The aim of the present study was to evaluate the role of intramuscular triglyceride (mTG) and FFA levels in insulin sensitivity in 30 nondiabetic normal-weight or obese subjects (18 with body mass index [BMI] = 21.8 +/- 3.3 kg/m2 and 12 with BMI = 34.6 +/- 2.7 kg/m2) who underwent minor abdominal surgery. Body composition was estimated by isotopic dilution, substrate oxidation by indirect calorimetry, and whole-body glucose uptake by euglycemic-hyperinsulinemic clamp (EHC). Glucose uptake (M) value negatively correlated with the MTG level (R2 = -.56, P < .0001), which was increased in obese patients (11.6 +/- 2.2 v 6.2 +/- 1.4 micromol/g wet weight muscle tissue, P < .0001). The TG fatty acid profile was significantly different in the 2 groups: an increased concentration of saturated fat was present in obese patients (unsaturated to saturated ratio, 1.89 +/- 0.40 v2.19 +/- 0.07, P < .0001). Stepwise linear regression analysis of total mTGs and palmitic and oleic fractions on the M value showed that only TGs and palmitic acid were significantly related to glucose uptake (R2 = .66, P < .0001). Furthermore, among the other anthropometric variables, only the BMI was significantly correlated with MTGs (R2 = .71, P < .0001). In conclusion, not only the MTG concentration but also the FFA pattern seems to affect insulin-mediated glucose uptake. A pivotal role might be played by a high saturated fatty acid content in the TGs.

Background: The course of chronic pancreatitis is often unpredictable and many factors are likely to be involved in the progression of the disease. In physiological condition, pancreatic juice exerts significant antibacterial activity, which is impaired in patients with chronic pancreatitis. Aim: Hypothesizing that Helicobacter pylori could, in these conditions, lead to an ascending infection, we aimed to assess the presence of H. pylori sequences in pancreatic juices of patients with chronic pancreatitis. Methods: 40 patients (mean age 52±3 yr) with alcoholic chronic pancreatitis and H. pylori infection were examined. Pancreatic juices were collected during endoscopic retrograde cholangiopancreatography. Using polymerase chain reaction (PCR) with two primers homologous to a portion of urease-C gene, H. pylori DNA was detected. Gastric biopsies, microscopically positive to H. pylori were used as positive controls. Results: All gastric biopsies produced H. pylori-specific DNA products. Conversely, no H. pylori urease-C gene sequences have been detected in any of the pancreatic juices. Conclusion: Our data suggest that the impaired antibacterial activity of pancreatic juices in patients affected by chronic pancreatitis does not have a permissive role for a superimposingH. pyloriinfection in the pancreas. The possibility that Helicobacter species other than pylori may be involved in a superimposing infection requires further investigation.

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Helicobacter pylori is one of four organisms often investigated for ari association with ischaemic heart disease. The four, including Chlamydia pneumoniae, Cytomegalovirus and Herpes virus, cause low-grade, life-long infections that can produce a persistent inflammation, the kind that leads to heart disease. Several studies suggest an association, but others suggest none. Patients with poor access to medical care are more likely to become infected and also more likely to suffer from coronary artery disease. Although the literature data are provocative and interesting, the two things may not be related. Helicobacter pylori infection is quite prevalent among individuals without ischaemic heart disease and absent in many of those with ischaemic heart disease. Thus, more definite answers about whether there is any link between Helicobacter pylori and cardiovascular disease are needed. It would be essential to establish the specific mechanisms that possibly confer vulnerability or protection toward coronaropathy. But a definite answer could come from clinical trials designed to test whether antibiotics can prevent the disease. Until now, no randomised trial has suggested a positive effect of Helicobacter pylori eradication in reducing the incidence of cardiac events.

The role of Helicobacter pylori in gastric carcinogenesis is supported almost exclusively by epidemiological data and prospective histopathological studies. From biological and molecular points of view, there is no evidence that H pylori or its cytotoxic products have any mutagenic effects. Nevertheless, this infection is associated with profound changes in the pattern of epithelial cell turnover in gastric glands, though the importance of these changes in gastric carcinogenesis is still controversial. H pylori infection increases cell proliferation and alters the distribution of cycling cells within these glands, but these changes can be reversed by successful eradication of the infection. Apoptosis seems to be increased in gastric epithelial cells during H pylori infection, as shown by in vitro studies. There is some, though no conclusive, evidence that this finding also occurs in H pylori positive subjects. It seems that cagA status influences the effect of H pylori on epithelial apoptosis in infected patients. An association of in vitro H pylori induced apoptosis with changes in the expression of pro- and anti-apoptotic genes is reported in the literature, but further study is necessary to clarify the effect of H pylori infection on the molecular events of the apoptotic pathway.

Mucosa-associated lymphoid tissue (MALT) develops in gastric mucosa in response to chronic antigenic stimulation, such as Helicobacter pylori infection. However, reactive lymphoid follicles have been found also in the stomach of H. pylori-negative coeliac patients, suggesting that other environmental factors may be involved in MALT genesis. The aim of our study was to evaluate the effects of gluten withdrawal in H. pylori-negative coeliac patients with gastric MALT.We studied 23 H. pylori-negative untreated coeliac patients with gastric MALT. All patients underwent determination of antigliadin (AGA) and antiendomysium antibodies (EMA) and upper endoscopy with multiple biopsies in duodenum, gastric corpus, and antrum. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. All patients were started on a gluten-free diet and were reevaluated after 12 months. To consider their adherence to the gluten-free diet we relied on direct patient questioning. Thirteen patients who had strictly adhered to the gluten-free diet constituted our study group. Ten patients who had not strictly adhered to gluten withdrawal from their diet constituted the control group.Regression of MALT was obtained in 9 of 13 (69%) patients who strictly followed the gluten-free diet; in the control group MALT disappeared in 2 of 10 (20%) patients (P=0.0361).Disappearance of reactive lymphoid follicles in the gastric mucosa of H. pylori-negative coeliac patients after gluten withdrawal suggests that antigens related to alimentary gluten may constitute persistent stimuli for development of gastric MALT in coeliac patients.

The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation.Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release.During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats.The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Raynaud's phenomenon is defined by anintermittent vasospasm of the arterioles of the distallimbs. Helicobacter pylori infection has been recentlyassociated with Raynaud's phenomenon. The aim of this study was to assess the effects of H. pylorieradication on Raynaud's attacks. Forty-six patientsaffected by primary Raynaud's phenomenon were evaluated.H. pylori infection was assessed by [13C]urea breath test. Eradication therapy was given toinfected patients for seven days. Discomfort and theduration and frequency of attacks of Raynaud'sphenomenon per week were assessed. Thirty-six subjectswere infected with H. pylori; the bacterium waseradicated in 83% of these after therapy. Attacks ofRaynaud's phenomenon completely disappeared in 17% ofthe patients with H. pylori eradication. Discomfort and the duration and frequency of attacks ofRaynaud's phenomenon were significantly reduced in 72%of the remaining patients. Conversely, attacks ofRaynaud's disease did not change significantly during the 12-week follow-up period either in the H.pylori-negative patients or in the infected subjects inwhom the bacterium was not eradicated by therapy. Thestudy shows that H. pylori eradication causes a significant decrease in clinical attacks ofRaynaud's disease. The reduction of vasoactivesubstances determined by the eradication of thebacterium may be the pathogenetic mechanism underlyingthe phenomenon.

Surveillance of cirrhotic individuals for early detection of HCC, based on ultrasonography (US) and alpha1-fetoprotein (AFP) determination, is a recommended practice currently applied also to elderly patients. However, several age-related factors may jeopardize the results of surveillance in these patients. Aim of the study was to evaluate the benefit of surveillance for HCC in elderly individuals.Multicenter retrospective study on 1,277 consecutive patients with HCC. The inclusion criteria were: underlying chronic liver disease, description of cancer stage, and modalities of its diagnosis. Among the 1,037 patients fulfilling these criteria, 363 agedor = 70 yr were considered.The tumor was detected during surveillance, based on US and AFP performed every 6-12 months, in 158 individuals (group 1), incidentally in 138 (group 2) and because of symptoms in 67 (group 3). Surveillance reduced the risk of dealing with an advanced cancer (odds ratio (95% Confidence Interval): 0.18 (0.09-0.37) vs group 3, and 0.29 (0.17-0.49) vs group 2). The frequency of effective treatments decreased from group 1 to group 3 (73%, 57%, and 31%, respectively). The main cause of death was HCC progression. The survival corrected for the lead time of group 1 (median: 24 months) was significantly better than the crude survival of group 3 (7 months; p= 0.003) and barely better than that of group 2 (21 months). The latter also showed a better prognosis with respect to group 3 (p= 0.018).Surveillance for HCC improves the survival of elderly cirrhotic patients by expanding the percentage of cancers amenable to effective treatments.

Antiphospholipid syndrome is a disorder characterised by recurrent venous or arterial thrombosis and/or foetal losses associated with typical laboratory abnormalities. The initial manifestation of anthiphospholipid syndrome can involve many organ systems either singly or in combination. We describe the case of a 62 year old female showing schizophrenia-like symptoms in which further evaluations allowed us to diagnose the antiphospolipid syndrome.

Background: Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. Aims: The present study was designed to define the role of nutrition in gastroenterology departments by means of two investigations analyzing: a) the availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: the incidence and frequency of indications for its use, together with the type of treatment adopted. Patients and Methods: Two questionnaires were sent to Italian Academic and Hospital gastroenterology Departments, all with clinical wards. Results: The results obtained refer to 27 Departments, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two weeks of the study. The first analysis shows that clinical nutrition and outpatients nutritional treatment are carried out in 73% of University hospitals and 46% of State hospitals. There are areas devoted specifically to nutritional treatment in 35% of the total departments, while 42% have an operative multidisciplinary nutritional team". The use of artificial nutrition is confirmed in 81% of the departments, preparation of the parenteral nutrition bags being carried out autonomously in 50% of them, by the hospital pharmacy in 39%, by other wards in by other wards in 12% and by private pharmaceutical companies in 12%. Finally, our data show that scales and the statiometer are available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the departments, and calorie intake can be assessed in 22-41%. The second analysis revealed that nutritional treatment was necessary in 50% of patients in the case series examined and that this was taken into account and given in almost all cases (91%). In detail, 69% of the patients treated received dietetic supplementation and 31% artificial nutrition, (12% enteral; 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. Conclusion: It could be stated that: i) artificial nutrition is commonly used in gastroenterology departments in Italy; ii) the indications for enteral and parenteral nutrition are not always properly respected: There is excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iii) nutritional treatment is often given without adequate nutritional assessment confirmed by the relative technological tools. A better awareness of correct practices for nutritional support should be promoted, encouraging both greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology.

Iron is an important metal in the complex biochemistry in human beings. However there are primary or secondary diseases that lead to an accumulation of iron in parenchymal organs and induce progressive and serious systemic harm. This review aims to define the fundamental steps of cell biology and physiology of iron and the pathophysiological mechanisms responsible for its accumulation in the parenchyma. In addition, we analyze the main primitive (hemochromatosis) and secondary (inflammation, liver diseases and hematological) diseases, responsible for the damage caused by iron, and we analyze the clinical consequences of iron overload. Furthermore, we pass under review a particular classification of general mechanisms and kinetics of iron overload responsible for its clinical phenotypes, dividing them into systemic, cellular and subcellular overload mechanisms. Finally we describe the main pathologic stages resulting from iron overload, with particular reference to liver damage and progression to hepatocellular carcinoma.

Management of functional dyspepsia is still controversial. Different controlled trials reported a superiority of prokinetics, H2-receptor antagonists and proton-pump inhibitors over placebo; nevertheless, symptomatic improvement after therapy is often incomplete and some of these drugs possess serious side effects. The aim of the study was to evaluate the efficacy of a new medical device in respect to domperidone in patients with functional dyspepsia.In a cross-over, randomized trial, 36 patients with functional dyspepsia ingested two daily doses of a medical device (Digerfast) or domperidone (Peridon) for 21 days. Clinical evaluation was performed at baseline (T0) and after 21 days (T1) for each treatment. A Visual Analogue Scale (VAS) and the generic scale 36-item Short Form (SF-36) were used to assess symptom intensity and changes in health-related quality of life, respectively.At T0 no statistical difference was found for each symptom between medical device and domperidone. At T1 both treatments significantly improved in respect to baseline values all the evaluated gastrointestinal symptoms (P0.5 for all comparisons) except for vomiting. No difference in gastrointestinal symptoms between the two treatments was found at T1. Regarding SF-36 evaluation, at T0 no statistical differences were found for each SF-36 parameter between the two regimens. At T1 both treatments significantly improved most of the evaluated SF-36 parameters in respect to baseline values. No difference in SF-36 parameters between the two treatments was found at T1.Both the medical device and domperidone significantly improved gastrointestinal symptoms and quality of life in subjects with functional dyspepsia, not showing significant difference in efficacy.

Although small bowel nonendocrine neoplasms are rare, their incidence has increased dramatically over the past 30 years. Small bowel malignacies can be classified depending upon their cellular origin into four principal histotypes: carcinoid tumors, adenocarcinomas, lymphomas and mesenchymal tumors. Until a few years ago, the treatment of small bowel tumors had remained relatively unchanged, with little progress in the development of effective adjuvant therapies and in the improvement of long-term survival over time. Recently, the growing interest in the understanding of the mechanisms underlying carcinogenesis has offered novel insights for the diagnosis and therapy of small bowel tumors. This review summarizes the state-of-the-art of small bowel nonendocrine tumors and the recent advancements in the knowledge of their molecular pathogenesis and cellular origin, with particular emphasis on stem cell research field.

"Functional dyspepsia" represents a clinical condition of pain and/or persistent or recurrent discomfort that concerns a large portion of the healthy population. It has already been shown that some herbs (Melissa Officinalis, Cynara scolymus) can have favorable effects on digestion. The principal aim of this study is to determine whether the ingestion of "Gran Soleil" dessert, with or without herbs, after meals can be beneficial to health in subjects suffering from functional dyspepsia. For this purpose, thirty subjects with functional dyspepsia were enrolled and were asked to consume "Gran Soleil" with or without herbs; these subjects reported the course of their symptoms on VAS scale, during the basal period and after the ingestion "Gran Soleil" with and without herbs. It has been shown that the ingestion of "Gran Soleil" without herbs can induce a reduction both in the number of events connected to a dyspeptic syndrome and in their intensity; moreover the assumption of "Gran Soleil" with the addition of herbs helped to intensify this effect.

Amyloidosis is a rare disease caused by extracellular deposits of insoluble fibrillar proteins in various organs and tissues. There are different forms of amyloidosis distinguished by the type of protein fibrils, by the sites of deposition and by associated conditions. Gastrointestinal involvement is common both in primary and secondary amyloidosis, while isolated gastrointestinal amyloidosis is rare. We describe a case of AL amyloidosis with a gastrointestinal involvement and restrictive cardiomiopathy. A 64 year old woman came to our attention with a history of chronic diarrhoea and weight loss, associated with dysphagia, dry mouth, xerophtalmia, chronic gastritis and depression. Clinical diagnosis has been difficult because of aspecificity of symptoms that mimed other more common diseases, like gastro-paresis, epigastric discomfort, gastric or duodenal ulcers, perforation, malabsorption, intestinal pseudo-obstruction. There is an important risk of misunderstanding and diagnostic delay. Indeed in this patient a diagnosis of irritable colon syndrome was erroneously established two years before admission in our hospital. Therefore gastrointestinal amyloidosis should be considered among differential diagnoses of chronic diarrhoea and weight loss when other more common diseases have been excluded.

Familial Mediterranean Fever (FMF) is the most frequent periodic febrile syndrome among the autoinflammatory syndromes (AS), nowadays considered as innate immunity disorders, characterized by absence of autoantibodies and autoreactive T lymphocytes. FMF is a hereditary autosomal recessive disorder, characterized by recurrent, self-limiting episodes of short duration (mean 24e72 h) of fever and serositis. In FMF, periodic attacks show inter- and intra-individual variability in terms of frequency and severity. Usually, they are triggered by apparently innocuous stimuli and may be preceded by a prodromal period. The Mediterranean FeVer gene (MEFV) responsible gene maps on chromosome 16 (16p13) encoding the Pyrine/Marenostrin protein. The precise pathologic mechanism is still to be definitively elucidated; however a new macromolecular complex, called inflammasome, seems to play a major role in the control of inflammation and it might be involved in the pathogenesis of FMF. The most severe long-term complication is type AA amyloidosis, causing chronic renal failure. Two types of risk factors, genetic and non-genetic, have been identified for this complication. Currently, the only effective treatment of FMF is the colchicine. New drugs in a few colchicine resistant patients are under evaluation

In autoimmune disorders (ADs), if Hepatitis C Virus (HCV) is present, immunosuppressive treatment could increase virus replication. Cyclosporine A (CsA), in standard therapeutic doses, has been proven able to inhibit HCV cyclophilin in vitro. Therefore CsA could improve the therapy of HCV patients with ADs.In these patients, we started an open pilot study to evaluate the safety of 3 mg/kg CsA and the ability to reduce steroid therapy.Five females and 1 male were recruited; mean age 66 +/- 8 years, mean disease duration 13 +/- 5 years. Three patients are affected by Psoriasic Arthritis, 1 by Rheumatoid Arthritis, 1 by Sjogren Syndrome, and 1 by Myasthenia Gravis. None of them had chronic active hepatitis. HCV genotypes were type 2 (in 3 cases) and type 1 (in 3 cases). Patients were treated with 3 mg/kg of CsA for a period of time ranging from 6 to 12 months. The starting mean dose of prednisone was 12.5 mg/day. Liver function tests were checked monthly and serum HCV-RNA load was checked by RT-PCR before and 2 months into the therapy.The prednisone dose was reduced from 12.5 mg/day to 7.5 mg/day. The aminotransferases levels were unchanged after 6 months. In patients with low HCV-RNA levels before treatment, no modifications of viral load were observed, whereas patients with increased levels at onset showed mild reduction 2 months into the treatment.Immunosuppressive treatment of ADs patients with HCV infection can be safely provided with the integration of CsA.

Sarcoidosis is a granulomatous disease of unknown origin, with pulmonary findings in more than 90% of patients. Extrapulmonary involvement is common and all organs can be involved (especially lymph nodes, eyes, joints, central nervous system) but it is rare to find an isolated extrapulmonary disease (less than 10% of patients). Granulomatous inflammation of the spleen and the liver is common in patients with systemic sarcoidosis, while hepatosplenic enlargement is unusual and splenic involvement rare. We report two cases of systemic sarcoidosis, that onset with splenic and hepatosplenic disease, and one case with splenic sarcoidosis without pulmonary involvement. In the first case a 53-year-old woman with mild abdominal pain underwent sonography and CT, which revealed one hypoechoic/hypodense splenic lesion. Laboratory tests were normal. In order to exclude a lymphoma, splenectomy was performed: histology revealed a sarcoid granuloma. After surgery the patient was asymptomatic and now, after two years, disease is silent. The second case is a 66-year-old woman with a recent weight loss (8 kg in two months) and alterated liver function tests (AST 61 U/l, ALT 72 U/l, Alkaline phosphatase 748 U/l, g-GT 381 U/l). Since she had a familiar history of colon cancer, abdominal US scan, abdominal CT scan and MRI were performed and showed inter-aorto-caval lymphadenopathies and discreet multiple bilobar hepatic and splenic substitutive lesions, with no signs of primary tumor. Upper and lower GI endoscopy, full gynecological workup, complete set of tumor markers, bone marrow biopsy were performed. All resulted negative for neoplasia. Small pulmonary infiltrations were observed on chest-CT scan but cytology on BAL was normal. Infections were also excluded. An exploratory laparotomy showed whitish peritoneal, hepatic and splenic nodules. The histological exam revealed chronic granulomatous lesions typical for sarcoidosis. During a two-year follow-up after the splenectomy the patient feels well without any treatment. The third patient is a 32-year-old woman with mild epigastric pain after meals. Neck-thoracic CT, bone scintigraphy and upper GI endoscopy were negative. Abdominal US and MR showed splenomegaly with multiple splenic lesions. Splenectomy was performed and histological exam showed chronic granulomatous lesions typical for sarcoidosis. Further laboratory tests were normal, except for ACE (66 UI/l). After the surgery ACE became normal and now, three years later, the patient is still asymptomatic. We conclude that hepatosplenic involvement is less rare than it is thought. It is often oligosymptomatic or accompanied with unspecific manifestations and laboratory abnormalities. The diagnosis could be difficult; in fact typical laboratory findings of sarcoidosis such as ACE, lysozyme, calcium, were not diagnostic. Ultrasonography and CT were important but the diagnosis was established only with the histological examination of suspected lesions. This latter required to differentiate liver and/or spleen sarcoidosis from tuberculosis and other infections, primary biliary cirrhosis, metastasis or malignant lymphoma.

Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular.The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases.Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group.The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

A good digestion is essential to maintain a healthy status. It is known that physiological digestive processes could be improved by the ingestion of some medicinal plants, while specific foods can facilitate the occurrence of gastrointestinal symptoms. Moreover, sensory properties of food seem to also influence digestion. We assessed the influence on physiological digestive processes of two Gran Soleil (GS) products containing a mixture of digestive plant extracts, citrus juices and liquors. We evaluated, in 10 healthy volunteers, the eventual occurrence of gastrointestinal symptoms after their ingestion and measured their palatability. Ingestion of GS did not cause significant gastrointestinal symptoms. Moreover, the palatability median score shows a good appreciation of the products. In conclusion, it is possible to suppose that a product with a good palatability, able to support and maintain a good digestive condition, derives from the mixture of digestive herbs, citrus juices, liquor and other ingredients.

To evaluate state and trait form of anxiety and current depression in patients affected by gastrointestinal diseases.We studied 1641 outpatients with gastrointestinal disorders, consecutively referred to our Internal Medicine outpatients from 1997 to 2005. State and trait anxiety were assessed by the State and Trait Anxiety Inventory. Current depression was assessed by the Zung self-rating depression scale.Among patients, 1379 (84.1%) showed state anxiety, 1098 (67%) showed trait anxiety and 442 (27%) showed current depression. The number of gastrointestinal diseases was directly correlated to state anxiety (p0.001) and trait anxiety (p = 0.04). Females showed higher levels of anxiety and depression than males (p0.001). State anxiety was related to food allergies (p0.001), small intestinal bacterial overgrowth (SIBO) (p = 0.001), Hp infection (p = 0.01) and ulcerative colitis in active phase (p = 0.03). Trait anxiety was related to irritable bowel syndrome (IBS) (p0.001), Helicobacter pylori (Hp) infection (p = 0.001), food allergies (p = 0.001) and SIBO (p = 0.001). Current depression was related to IBS (p0.001) and coeliac disease (p = 0.01), SIBO (p = 0.02). A predicted probability of 0.77 +/- 0.16 to have state anxiety, of 0.66 +/- 0.12 to have trait anxiety and of 0.39 +/- 0.14 to have depression was found in these patients.Most of the patients who seek medical consultation for gastrointestinal problems show an associated affective disorder. These patients should be managed by a team including gastroenterologists, psychologists and/or psychiatrists, or by a gastroenterologist having expertise in the treatment of psychological disorders.