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Urine-derived renal epithelial cells (URECs) are highly voided after kidney transplant and express typical kidney markers, including markers of kidney epithelial progenitor cells. Recently URECs have shown promising immunomodulatory properties when cultured with Peripheral Blood Mononuclear Cells (PBMCs), promoting an increase in the T regulatory cells. In vivo, kidney cells are highly exposed to damage associated molecules during both acute and chronic kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most -known early marker of acute and chronic kidney damage. However, its role on the evolution of renal damage has not yet been fully described, nor has its impact on the characteristics of renal-derived cells during in vitro culture. The aim of this study is to investigate the effect of NGAL on the characteristics of URECs isolated after kidney transplant, by exposing these cells to the treatment with NGAL during in vitro culture and evaluating its effect on UREC viability, proliferation, and immunomodulatory potential. The exposure of URECs to NGAL reduced their viability and proliferative capacity, promoting the onset of apoptosis. The immunomodulatory properties of URECs were partially inhibited by NGAL, without affecting the increase of Treg cells observed during UREC-PBMCs coculture. These results suggest that the exposure to NGAL may compromise some features of kidney stem and specialized cell types, reducing their viability, increasing apoptosis, and partially altering their immunomodulatory properties. Thus, NGAL could represent a target for approaches acting on its inhibition or reduction to improve functional recovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objectives: Since the beginning of the COVID-19 pandemic, changes in the circulation of respiratory viruses have been observed after measures to control the spread of SARS-CoV-2 were implemented. In this sense, we aimed to understand the circulation of the respiratory virus and its impact in a controlled healthy population of healthcare professional (HCP) volunteers in phase III of the clinical trial of the ChadOx nCoV1 conducted in São Paulo, Brazil., Study Design: This was a nested observational cohort study within a clinical trial., Methods: We performed RT-qPCR to detect SARS-CoV-2, influenza virus A and B (IVA and IVB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (hMPV), human coronaviruses (hCoVs: HKU-1, NL63, OC43, and 229-E), parainfluenza virus (PiV) I-IV, and q-PCR for adenovirus in nasopharyngeal and oropharyngeal samples obtained from HCP enrolled in the clinical trial to assess respiratory viruses infection among vaccinated and non-vaccinated., Results: From July 2020 to January 2022, 876 samples were included from 737 volunteers (median age: 33 years, 62.9% female). New episodes were registered for 119 individuals. We observed an overall positivity of 37.7% for SARS-CoV-2 and 16.4% for other respiratory viruses; HRV was the second most detected virus (8%), followed by RSV (2.4%). Fully vaccinated individuals accounted for 53.3% of collected samples, and 52.9% presented at least one respiratory virus infection, with SARS-CoV-2 being the most predominant etiologic agent (62.3%). Influenza and hMPV were not detected among the tested samples. Among the subjects that presented more than one episode, SARS-CoV-2 and HRV infections were related to direct contact with patients (P < 0.002)., Conclusions: Data show high infection rates among HCPs even under mask policies and contact precautions, highlighting the need for improvement in infection control measures in this population regardless of the vaccination program., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Suspected small bowel bleeding (SSBB) is the main indication for videocapsule endoscopy (VCE) and double balloon enteroscopy (DBE). We assessed the impact of both modalities in a large cohort of SSBB patients in a European tertiary center., Methods: We retrospectively evaluated consecutive patients with SSBB undergoing VCE and/or DBE from March 2001 to July 2020. Demographic/clinical parameters, anticoagulant therapies, technical characteristics and adverse events were collected, as well as diagnostic yield (DY), VCE-DBE concordance, hemoglobin (Hb) values before and after DBE, and complications., Results: 807 VCEs and 407 DBEs were performed in 751 patients. The DY was significantly higher in DBE compared with VCE (68.8% vs 57.7%), with the highest (75%) yield for overt active SB bleeding. The agreement between VCE and DBE was generally suboptimal (k = 0.059). This improved in cases where both procedures were done within 1-5 days of the other (k = 0.323). Post-procedural Hb values were significantly higher. In patients treated with direct oral anticoagulants (DOACs), there were no differences in DY, complications or Hb values compared with non-DOAC patients., Conclusion: VCE and DBE play a pivotal role in the diagnostic and therapeutic approach to SSBB, having a high clinical impact even in patients treated with DOACs., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Intestinal ultrasound (IUS) examination is a first-line non-invasive imaging procedure for patients with suspicion of bowel diseases., Aim: To assess the feasibility, reproducibility and diagnostic accuracy of a pocket-size ultrasound device (PUD) in identifying the presence of intestinal alterations in patients consecutively recruited to undergo IUS examination., Methods: 200 consecutive patients (57% female, 48.8 years) underwent both PUD (two independent investigators) and IUS examination on the same day. Nine ultrasonographic signs were systematically searched for. PUD inter-observer reproducibility was assessed by kappa statistic and ICC. The diagnostic accuracy of PUD as compared to IUS results was assessed by calculating sensitivity, specificity and corresponding positive and negative likelihood ratios., Results: PUD and IUS examinations were successful in 100% of the patients. PUD reproducibility was good/excellent at evidencing the presence (ICC 0.84) and length (ICC 0.85) of an intestinal tract with thickened wall and abdominal free fluid (ICC 0.87). The diagnostic accuracy of PUD, compared to traditional IUS, was good with regard to the presence of bowel wall thickening (sensitivity 92%, specificity 95%), the length of the thickened bowel (sensitivity 94%, specificity 95%) and the presence of free fluid (sensitivity 81%, specificity 99%)., Conclusions: PUD is a feasible, reproducible and accurate first-line screening tool for the assessment of the gastro-intestinal tract., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: To date no studies evaluated liver stiffness and pancreatic stiffness by shear-wave elastography, in alcoholic liver disease setting., Aims: To assess feasibility and reproducibility of Shear-wave elastrography in measuring liver and pancreatic stiffness in alcoholic liver disease and investigate the correlation among liver and pancreatic stiffness and clinical data., Methods: Liver and pancreatic stiffness were measured by elastography (2 examiners) in patients with alcoholic liver disease and in healthy volunteers, for reference values. Effect of clinical data was evaluated on log-transformed pancreatic or liver stiffness, using univariate and multivariate linear regression model., Results: 87 patients and 46 healthy volunteers enrolled. Both the stiffness values were higher in patients than healthy volunteers (p < 0.001). For liver stiffness: no failure measurements found, the Intraclass correlation coefficient (between 2 examiners) was 0.72 and the variables significantly correlated at multivariate analysis were cirrhosis (p < 0.0001) and steatosis (p = .007). For pancreatic stiffness: 2 failures found, with ICC 0.40 and the only variable significantly correlated at multivariate analysis was liver cirrhosis (p = .005)., Conclusions: Shear-wave elastography feasibility was good for liver and pancreatic stiffness. Reproducibility was good for liver stiffness, whereas fair for pancreatic one. Both the stiffness correlated with alcoholic liver disease severity. Elastography could be a useful tool to detect and monitor alcohol-related liver and pancreatic damage., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Sodium channel myotonia and paramyotonia congenita are caused by gain-of-function mutations in the skeletal muscle voltage-gated sodium channel hNav1.4. The first-line drug is the sodium channel blocker mexiletine; however, some patients show side effects or limited responses. We previously showed that two hNav1.4 mutations, p.G1306E and p.P1158L, reduce mexiletine potency in vitro, whereas another sodium channel blocker, flecainide, is less sensitive to mutation-induced gating defects. This observation was successfully translated to p.G1306E and p.P1158L carriers. Thus, the aim of this study was to perform a pharmacological characterization of myotonic Nav1.4 mutations clustered near the fast inactivation gate of the channel. We chose seven mutations (p.V1293I, p.N1297S, p.N1297K, p.F1298C, p.G1306E, p.I1310N, and p.T1313M) from the database of Italian and French networks for muscle channelopathies. Recombinant hNav1.4 mutants were expressed in HEK293T cells for functional and pharmacological characterization using the patch-clamp technique. All the studied mutations impair the kinetics and/or voltage dependence of fast inactivation, which is likely the main mechanism responsible for myotonia. The severity of myotonia is well-correlated to the enhancement of window currents generated by the intersection of the activation and fast inactivation voltage dependence. Five of the six mutants displaying a significant positive shift of fast inactivation voltage dependence reduced mexiletine inhibition in an experimental condition mimicking myotonia. In contrast, none of the mutations impairs flecainide block nor does p.T1313M impair propafenone block, indicating that class Ic antiarrhythmics may constitute a valuable alternative. Our study suggests that mutation-driven therapy would be beneficial to myotonic patients, greatly improving their quality of life., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM)., Aims: To evaluate oesophageal motility by HRM in patients with idiopathic CIPO., Methods: 14 patients with idiopathic CIPO underwent oesophageal HRM. Multiple rapid swallows (MRS) were performed in order to evaluate contraction reserve. The Chicago Classification 3.0 was used to classify the oesophageal motility disorders., Results: One idiopathic CIPO patient had type-II achalasia, one aperistalsis and 12 had minor disorder of peristalsis (11 ineffective oesophageal motility and one fragmented peristalsis). These minor disorders were not significantly different from those of 50 other consecutive patients who underwent HRM for dysphagia or GERD and received the diagnosis of ineffective oesophageal motility. Three of the 12 idiopathic CIPO patients with minor disorder of peristalsis had no contraction reserve after MRS., Conclusions: HRM is able to identify different grades of oesophageal motor impairment in patients with idiopathic CIPO. Presence of major oesophageal dismotility or absent contraction reserve suggest a more severe and widespread motor disorder., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The incidence of gastroenteropancreatic neuroendocrine neoplasms has increased in the recent decades. An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published mostly between year 1997 and June 2017, using both medical subject heading (MeSH) terms and free-language keywords about the accuracy and diagnostic and therapeutic role of endoscopic ultrasound in the context of gastro-entero-pancreatic neuroendocrine neoplasms. Endoscopic ultrasound is the modality of choice for diagnosing pancreatic neuroendocrine neoplasms and for the locoregional staging of gastric, duodenal, pancreatic and rectal neuroendocrine neoplasms; in particular, in the setting of pancreatic neuroendocrine neoplasms it has demonstrated higher accuracy in tumor detection than other imaging modalities. Furthermore, the possibility of tattooing pancreatic lesions by endoscopic ultrasound fine needle aspiration may help surgeons to locate the tumor and avoid any demolition surgery. Finally, endoscopic ultrasound-guided therapies have been proposed and used in several studies for patients unsuitable for surgery, with good results on the control of symptoms and the reduction of tumor burden., (Copyright © 2017. Published by Elsevier Ltd.)

Multidrug-resistant (MDR) bacteria are widespread in hospitals and have been increasingly isolated from aquatic environments. The aim of the present study was to characterize extended-spectrum β-lactamase (ESBL) and quinolone-resistant Enterobacteriaceae from a hospital effluent, sanitary effluent, inflow sewage, aeration tank, and outflow sewage within a wastewater treatment plant (WWTP), as well as river water upstream and downstream (URW and DRW, respectively), of the point where the WWTP treated effluent was discharged. β-lactamase (bla) genes, plasmid-mediated quinolone resistance (PMQR), and quinolone resistance-determining regions (QRDRs) were assessed by amplification and sequencing in 55 ESBL-positive and/or quinolone-resistant isolates. Ciprofloxacin residue was evaluated by high performance liquid chromatography. ESBL-producing isolates were identified in both raw (n=29) and treated (n=26) water; they included Escherichia coli (32), Klebsiella pneumoniae (22) and Klebsiella oxytoca (1). Resistance to both cephalosporins and quinolone was observed in 34.4% of E. coli and 27.3% of K. pneumoniae. Resistance to carbapenems was found in 5.4% of K. pneumoniae and in K. oxytoca. Results indicate the presence of bla CTX-M (51/55, 92.7%) and bla SHV (8/55, 14.5%) ESBLs, and bla GES (2/55, 3.6%) carbapenemase-encoding resistance determinants. Genes conferring quinolone resistance were detected at all sites, except in the inflow sewage and aeration tanks. Quinolone resistance was primarily attributed to amino acid substitutions in the QRDR of GyrA (47%) or to the presence of PMQR (aac-(6')-Ib-cr, oqxAB, qnrS, and/or qnrB; 52.9%) determinants. Ciprofloxacin residue was absent only from URW. Our results have shown strains carrying ESBL genes, PMQR determinants, and mutations in the gyrA QRDR genes mainly in hospital effluent, URW, and DRW samples. Antimicrobial use, and the inefficient removal of MDR bacteria and antibiotic residue during sewage treatment, may contribute to the emergence and spreading of resistance in the environment, making this a natural reservoir., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The implementation of cross-sectional imaging techniques for the clinical management of Crohn's disease patients has steadily grown over the recent years, thanks to a series of technological advances, including the evolution of contrast media for magnetic resonance, computed tomography and bowel ultrasound. This has resulted in a continuous improvement of diagnostic accuracy and capability to detect Crohn's disease-related complications. Additionally, a progressive widening of indications for cross-sectional imaging in Crohn's disease has been put forward, thus leading to hypothesize that in the near future imaging techniques can increasingly complement endoscopy in most clinical settings, including the grading of disease activity and the assessment of mucosal healing or Crohn's disease post-surgical recurrence., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Changes in the distribution and products of enteroendocrine cells may play a role in immune activation and regulation of gut inflammation. This review aims at critically evaluating the main enteroendocrine markers in inflammatory bowel diseases (IBD). A narrative review was performed by searching inflammatory bowel diseases and enteroendocrine biomarkers in PubMed. Relevant modifications of some enteroendocrine markers, such as Chromogranin A, and their correlation with disease activity have been reported in patients with inflammatory bowel diseases. Even if data about neuroendocrine markers are sometimes contrasting, they may be potentially useful for the diagnosis and clinical management of these patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Celiac disease is the most common autoimmune enteropathy in Western countries, and is usually associated with a good response to the gluten free diet and an excellent prognosis. However, a minority of patients develop complications of the disease, such as refractory celiac disease, ulcerative jejunoileitis and neoplastic complications such as adenocarcinoma of the small bowel and enteropathy associated T cell lymphoma. Neoplastic complications described in association with celiac disease have a high mortality rate, due to their aggressive behavior and to the usual advanced stage at the time of diagnosis. In recent years, the detection of small bowel lesions has dramatically improved thank to the availability of highly performing radiologic and endoscopic techniques. The diagnostic delay of malignant complications in patients with celiac disease may be improved by establishing a pragmatic flowchart for the identification and follow up of "at risk" patients. We performed a comprehensive review of the articles published on this issue in order to promote a roadmap to be applied when facing with celiac patients with suspected small bowel complications., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Genetic alterations suitable for targeted therapy are poorly known issues in pulmonary sarcomatoid carcinoma (PSC), an uncommon and life-threatening family of non-small cell lung cancers., Methods: Ninety-eight PSCs were assessed for MNNG HOS Transforming gene (MET) and anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by fluorescence in situ hybridization (FISH) and for relevant protein expression by immunohistochemical analysis, also taking advantage of phosphorylated (p-) antibodies. Moreover, levels of ALK and MET mRNA were also determined by real-time polymerase chain reaction and Western blot analysis for downstream activation pathways involving p-MET, p-protein kinase B, p-mitogen-activated protein kinase, p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase (p-FAK)., Results: MET amplification was detected by FISH in 25 of 98 PSCs (25.6%) and ALK amplification (but not the relevant rearrangement) was found in 16 of 98 (16.3%), with all ALK-amplified tumors also showing MET amplification (p < 0.0001). Nine PSCs, however, showed MET amplification without any ALK gene alteration. ALK protein expression was always lacking, whereas MET and p-MET were confined to the relevant amplified tumors only. Increased levels of ALK and MET mRNA were detectable in tumors with no direct relationship between mRNA content, protein expression, or alterations detected by FISH. Western blot assays showed complete activation of downstream signal pathways up to p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase recruitment in MET and ALK-coamplified tumors only, whereas isolated MET amplification, MET and ALK borderline amplification (5%-10% of tumor cells with ≥15 copies of the relevant gene), or negative tumors showing eusomy or chromosome polysomy were confined to p-mitogen-activated protein kinase, p-protein kinase B, and/or p-MET activation. Multivariate survival analysis pushed a higher percentage of MET altered cells or a higher value of MET copy gain per cell to marginally emerge for overall survival (p = 0.140) and disease-free survival (p = 0.060), respectively., Conclusions: ALK and MET seemed to act as synergistic, nonrandom coactivators of downstream signal when coamplified in a subset of patients with PSC, thus likely suggesting a combined mechanism of oncogene addiction. These alterations could be a suitable target for therapy based on specific inhibitors., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Ultrasound imaging is used to assess bowel abnormalities in gastrointestinal diseases. We aimed to assess the rate of predefined bowel ultrasound signs and their relationship with gastrointestinal symptoms and the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in cystic fibrosis patients in regular follow-up., Methods: Prospective study of 70 consecutive patients with cystic fibrosis and 45 controls who underwent abdominal ultrasound; pertinent findings were related to gastrointestinal symptoms and, in cystic fibrosis patients, to pancreatic status, malabsorption degree, lipase intake, CFTR genotype (classified as severe or mild against functional class of CFTR mutations)., Results: 96% patients showed at least one abnormal bowel ultrasound sign. Most frequent signs were lymph node enlargement (64%), bowel loop dilatation (55%), thick corpuscular intraluminal content (49%), bowel wall hypervascularization (26%), thickened bowel wall (22%) and intussusception (17%). Patients with recurrent abdominal pain showed more bowel wall hypervascularization than patients without recurrent pain (47% vs. 19%, respectively; p = 0.02) and intussusception (58% vs. 17%, respectively; p < 0.01). Genotype was not associated to specific bowel ultrasound signs. Patients with bowel loop intussusception showed greater lipase intake than those without intussusception (8.118 ± 2.083 vs. 5.994 ± 4.187, respectively; p < 0.01)., Conclusion: Cystic fibrosis patients present a higher rate of bowel ultrasound abnormalities than controls. Bowel ultrasound abnormalities are associated with abdominal symptoms., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Optimal management and treatment of type-1 gastric carcinoids is under debate., Aims: This prospective study evaluates the outcome of patients with recurrent type-1 gastric carcinoids treated with somatostatin analogues., Methods: From 2000 to 2013, among a population of 107 chronic atrophic gastritis patients, 25 (20% males, median age 62 years) developed type-1 gastric carcinoids and underwent regular clinical and endoscopic follow-up (median 77 months, range 6-165) after the initial treatment. Those patients showing recurrent disease were treated with somatostatin analogues until carcinoid disappearance., Results: 12/25 patients (33% males, median age 65 years) showed recurrent gastric carcinoids and were treated with somatostatin analogues for a median duration of 12 months. Median gastrin and chromogranin A levels, which were 802 pg/mL and 33 U/L, respectively, decreased to 299 pg/mL (p=0.002) and 15.6 U/L (p=0.001) at the end of the treatment. Gastric carcinoids disappeared after a median length of treatment of 12 months. After a median time of 19.5 months from somatostatin analogues discontinuation, 4/12 patients (25% males, median age 56 years) showed a further recurrence. A new cycle of treatment was performed successfully., Conclusions: This study confirms that type-1 gastric carcinoids are a recurring disease and somatostatin analogues, administered on 12-month cycles, represent an effective treatment., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Malnutrition is common in alcoholic liver disease and is associated with high rates of complications and mortality. In this article, the current literature was reviewed to highlight the relevance of proper nutritional management providing levels of evidence, when available. A PubMed search was performed for English-language publications from 1980 through 2014 with the keywords: alcoholic liver disease, nutritional deficiencies, nutritional support, enteral nutrition, parenteral nutrition, and protein-energy malnutrition. Manuscripts focused on nutritional approach in patients with alcoholic liver disease were selected. Although nutritional support for malnourished patients improves the outcome of hospitalization, surgery, transplantation and reduces the complications of liver disease and the length of hospital stay, specific guidelines are scanty. Both enteral and parenteral nutrition appear to improve nutritional parameters and liver function; however data on survival is often conflicting. As micronutrient depletion is common in alcoholic liver disease and each deficiency produces specific sequelae, all cirrhotic patients should be screened at baseline for deficiencies of micronutrient and supplemented as needed. In summary, protein-energy malnutrition and micronutrient depletion are clinical concerns in alcoholic liver disease. Nutritional therapy, including enteral nutrition, parenteral nutrition and micronutrient supplementation should be part of the multidisciplinary management of these patients., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: It has been suggested that multiple rapid swallowing should be added to oesophageal manometry., Aim: To prospectively evaluate whether 10 and 200 mL multiple rapid swallowing provide different information concerning motor function., Methods: 30 consecutive patients with oesophageal symptoms, 13 achalasia patients after successful pneumatic dilation and 19 healthy subjects performed eight 5 mL single swallows, two 10 mL and one 200 mL multiple rapid swallowing., Results: Almost all of the healthy subjects and two-thirds of the patients with oesophageal symptoms showed motor inhibition during both 10 and 200 mL multiple rapid swallowing. The oesophago-gastric pressure gradient was significantly higher during 200 mL multiple rapid swallowing within each group (p < 0.01), and significantly higher in the achalasia patients than in the other two groups (p < 0.0001). Presence of a contraction and increased contraction strength in comparison with single swallows were both more frequent after 10 mL than after 200 mL multiple rapid swallowing in the healthy subjects and the patients (p<0.05)., Conclusion: Motor inhibition could be similarly evaluated by means of 10 and 200 mL multiple rapid swallowing; 10 mL evaluated the after-contraction, whereas 200 mL multiple rapid swallowing was more valuable in identifying increased resistance to outflow., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.)

In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care. Digestive diseases were the first or second cause of hospitalizations in Italy in 1999-2009, with more than 1,500,000 admissions/year; however only 5-9% of these admissions was in specialized Gastroenterology units. Reported data show a better outcome in Gastroenterology Units than in non-specialized units: shorter average length of stay, in particular for admissions with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days); better case mix (higher average diagnosis-related groups weight in Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery units); lower inappropriateness of admissions (16-25% versus 29-87%); lower in-hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was 2.3% in Gastroenterology units versus 4.0% in others. The present document summarizes the scientific societies' official report, which constitutes the "White paper of Italian Gastroenterology"., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: A subset of celiac patients shows a high risk for small bowel malignancies., Aims: To select celiac patients considered at risk and evaluate the diagnostic yield of enteroscopy in this context., Methods: Celiac patients were enrolled from a tertiary referral centre during the period June 2011-June 2013, based on the following criteria: (i) patients diagnosed when aged 50+ and with poor response to gluten-free dieting; (ii) low dietary compliance; (iii) alarm symptoms. The patients underwent small bowel capsule endoscopy and/or double-balloon enteroscopy. Control populations were represented by the 165 non-celiac patients undergoing capsule endoscopy for obscure gastrointestinal bleeding, and the 815,362-strong population of the Italian province of Varese as a registered cohort., Results: Fifty-three patients (19% males, mean age 43.6±17.4 years) were evaluated. Two jejunal adenocarcinomas and one ileal neuro-endocrine tumour were diagnosed by enteroscopy (the diagnostic yield for malignancies in the selected population being 5.7%). In the non-celiac controls the detection rate of small bowel tumours by capsule endoscopy was 0.6% (P=0.04). When compared to the registered population, the relative risk for intestinal malignancy was 1282 (95% CI, 407-4033; P<0.0001)., Conclusions: Capsule endoscopy and double-balloon enteroscopy can be considered for early disease management of a subset of celiac patients., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Endoscopic ultrasonography is accurate, safe, and cost-effective in diagnosing common bile duct stones, thus suggesting the possibility to avoid invasive endoscopic retrograde cholangiopancreatography., Aim: To prospectively evaluate the diagnostic and therapeutic performance of early endoscopic ultrasonography in suspected choledocholithiasis., Patients and Methods: All consecutive patients presenting to the Emergency Department with suspicion of choledocholithiasis between January 2010 and January 2012 were evaluated and categorized as low, moderate, or high probability of choledocholithiasis, according to accepted criteria. Endoscopic endosonography was carried out within 48 h from the admission and endoscopic retrograde cholangiopancreatography was performed soon in case of confirmed choledocholithiasis., Results: Overall 179 patients were included: 48 (26.8%) were classified as low, 65 (36.3%) as moderate, and 66 (36.9%) as high probability of choledocholithiasis. Of the 86 patients with common bile duct stones at endoscopic endosonography, endoscopic retrograde cholangiopancreatography confirmed the finding in 79 (92%). By multivariate analysis only the common bile duct diameter proved an independent predictor of common bile duct stones., Conclusions: Early endoscopic endosonography is accurate in identifying choledocholithiasis allowing immediate endoscopic treatment and significant spare of unnecessary endoscopic retrograde cholangiopancreatography. This approach can be useful as a triage test to select patients not needing endoscopic retrograde cholangiopancreatography, allowing, in selected cases, their early discharge., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Malnutrition is common in inflammatory bowel diseases (IBD), mainly in Crohn's disease (CD) because the small bowel is primarily affected. We reviewed the literature to highlight the importance of proper nutrition management., Methods: A PubMed search was performed for English-language publications from 1999 through 2012. Manuscripts comparing nutritional approaches for IBD patients were selected., Results: We identified 2025 manuscripts: six meta-analyses, 170 clinical-trials, 692 reviews. The study findings are discordant. In adult CD, enteral nutrition plays a supportive role, steroid therapy remaining the first choice treatment. In CD children enteral nutrition may represent the primary therapy. As regards parenteral nutrition, there are no large randomized studies, although mild improvements in morbidity have been described as a result of parenteral nutrition in malnourished surgical IBD patients. Specific micronutrient deficiencies are common in IBD. A number of factors may contribute to micronutrient deficiencies, and these include: dietary restriction, disease activity and surgery. The possible therapeutic roles of omega-3 fatty-acids, probiotics and prebiotics have been studied, but the results are still preliminary., Conclusion: Protein-energy malnutrition and micronutrient depletion are clinical concerns in IBD patients. Enteral nutrition, parenteral nutrition and micronutrient supplementation are cornerstone of the multidisciplinary management of IBD patients., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Defensive medicine is becoming more frequent behaviour and has an impact on the economic 'health' of national healthcare systems., Aim: The aim of this study was to clarify the impact of defensive medicine on gastroenterological practices in Lombardy., Methods: Gastroenterologists attending the Lombardy Annual Gastroenterological Conference received a questionnaire based on multiple choice tests and visual analogue scales. The questionnaire was divided into three parts evaluating the respondent's characteristics, the number of procedures prescribed, and the percentage of those performed with a defensive purpose., Results: Sixty-four of 107 participants (60%) completed the questionnaire, 94% of whom reported practising defensive medicine. The percentage of defensively requested procedures amounted to 18% of all digestive endoscopies, 8.9% of abdominal ultrasonography scans, 4.9% of abdominal computed tomography or magnetic resonance scans, and 12.2% of all consultations. The total number of defensive procedures prescribed per month by the participants was 878, and 31.7% of the performed procedures (n=4897) were reported to defensively based. On the basis of the 2012 regional reimbursement fees, the yearly cost of defensive procedures prescribed and/or performed by all gastroenterologists in Lombardy was estimated to be € 8,637,835., Conclusions: Our findings indicate that defensive medicine profoundly affects current medical practices among gastroenterologists, and has a considerable economic impact., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Data about strategies for improving the diagnostic ability of capsule endoscopy readers are lacking., Aim: (1) To evaluate the detection rate and the interobserver agreement among readers with different experience; (2) to verify the impact of a specific training (hands-on training plus expert tutorial) on these parameters., Methods: 17 readers reviewed 12 videos twice; between the two readings they underwent the training. The identified small bowel findings were described by a simplified version of Structured Terminology and classifies as clinically significant/non-significant. Findings identified by the readers were compared with those identified by three experts (Reference Standard)., Results: The Reference Standard identified 26 clinically significant findings. The mean detection rate of overall readers for significant findings was low (about 50%) and did not change after the training (46.2% and 46.4%, respectively). There was no difference in the detection rate among readers with different experience. The interobserver agreement with the Reference Standard in describing significant findings was moderate (k = 0.44; CI95%: 0.39-0.50) and did not change after the training (k = 0.44; CI95%: 0.38-0.49) or stratifying readers according to their experience., Conclusions: Both the interobserver agreement and the detection rate of significant findings are low, regardless of the readers' experience. Our training did not significantly increase the performance of readers with different experience., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Hereditary hemochromatosis (HH) is most frequently related to homozygosity for the p.C282Y HFE mutation (C282Y(+/+)), hampering hepcidin induction in response to iron. The rs855791 polymorphism, encoding for the p.A736V variant of TMPRSS6 regulating hepcidin, influences iron status in the population. The aim of this study was to assess the influence of rs855791 on the penetrance and clinical expression of HH., Methods: We retrospectively considered 315 HH patients (163 C282Y(+/+), and 152 with other HFE genotypes) evaluated at the time of diagnosis, and 271 healthy controls with normal iron parameters, residents of Northern Italy; TMPRSS6 genotype was assessed by allele specific polymerase chain reaction., Results: The p.736V variant determining higher hepcidin release was under-represented in the patients (p=0.0023), independently of the presence of the C282Y(+/+) genotype, and the p.736V/V genotype protected from HH independently of age and sex (OR of HH for p.736A/A: 2.57, 1.3-4.1 and for p.736A/V: 1.84, 1.1-3.2). In the 96 C282Y(+/+) male patients without chronic viral hepatitis and alcohol abuse, the "high hepcidin" p.736V allele was negatively associated with cirrhosis independently of age, ferritin, ALT levels, and alcohol intake (OR 3.93, 95% C.I. 1.17-14.61 for the p.736A variant), and with the cumulative incidence of hepatocellular carcinoma (17% p.736A/A, 4% p.736A/V, 0 p.736V/V, p=0.05)., Conclusions: The p.A736V TMPRSS6 polymorphism is likely a modifier of HH expression. Additional studies are warranted to validate these findings in other cohorts and test their potential relevance for the clinical management of HH patients., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The advantages of using a computer-based simulator during colonoscopy training are debated. We aimed to explore its usefulness in objectively measuring trainees' competence in colonoscopy., Methods: Twelve colonoscopy trainees (fully trained in upper GI endoscopy) were evaluated using a computer-based simulator (GI-Mentor, Symbionix) before and during hands-on training (i.e. after 60 colonoscopies); the controls were 15 experts (>90% of caecal intubation). Both trainees and experts performed two "screening" simulations (easy and difficult) in a randomised order, and the time to reach the caecum and withdrawal time was assessed., Results: The percentage of caecal intubation progressively increased during hands-on training. All of the trainees intubated the caecum during the easy and difficult simulations, both before and during hands-on training. The median time (interquartile range) to reach the caecum upon easy simulation was the only variable influenced by hands-on training: 2.7 min (2.1-3.2) before and 1.9 min (1.6-2) during training (p<0.01). Withdrawal time was ≥6 min in the case of five trainees before training, and three during hands-on training. Computer-based simulator performance did not correlate with hands-on training performance., Conclusions: The computer-based simulator was not found to be useful in evaluating competence during hands-on training in colonoscopy., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Non-small-cell lung cancer remains the leading cause of cancer-related mortality in the United States and Europe. Most patients are diagnosed with metastatic disease for which chemotherapy remains the cornerstone of treatment. In non-metastatic disease, surgery is the most potentially curative therapeutic option, but its outcome is still poor, in particular for patients with lymph node involvement. Therefore, several randomized adjuvant/neoadjuvant trials using chemotherapy and/or radiotherapy investigated the possibility of increasing the overall survival of patients with surgically treated lung cancer. The findings are reviewed in this article., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: FHIT and p53 are the two most commonly altered tumor suppressor genes in lung cancer, and their molecular status regulates sensitivity to anticancer drugs. Although their functions are independent, there is evidence that their pathways might be interconnected, but little is known at the molecular level., Methods: Microarray profiling of FHIT-transduced lung cancer cells and modulation of FHIT levels by RNA interference in human bronchial cells were used to generate a signature of FHIT-regulated transcripts. Expression of these genes was evaluated by real-time polymerase chain reaction in 55 primary lung cancer samples characterized for FHIT and p53 expression by immunehistochemistry., Results: A signature of FHIT-transcripts, particularly enriched in genes involved in cell cycle control, was identified. This signature showed overlap with p53-regulated genes, indicating possible crosstalk between these proteins. Consistently, transcriptional deregulation after FHIT modulation was higher in p53-negative cells. In primary lung cancers, inactivation of either gene was detected in 48 of 55 cases (87%) and both genes in 23 of 55 (42%) cases, confirming the central role of these pathways. Primary tumors with inactivation of both FHIT and p53 displayed the strongest deregulation of growth-related pathways with high levels of expression of CCNB1, BUB1, CDC6, TOP2A, MCM6, and CENPF., Conclusions: FHIT and p53 seem to rely on common mediators, and inactivation of both genes results in prominent deregulation of growth-related pathways in lung cancer cell lines and primary tumors. This reveals crosstalk between these proteins and suggests a possible distinctive phenotype for tumors with inactivation of both genes.

The global spread of hepatitis B virus (HBV) and hepatitis C virus (HCV), their high chronicity rates and their progression to cirrhosis and hepatocellular carcinoma, are major public health problems. Research and intervention programmes for special population groups are needed in order to assess their infection risk and set up suitable prevention and control strategies. Aim of this paper is to give health care professionals information on HBV and HCV infections amongst migrants, drug users and prison inmates. The manuscript is an official Position Paper on behalf of the following Scientific Societies: Italian Association for the Study of the Liver (A.I.S.F.), Italian Society of Infectious and Tropical Diseases (S.I.M.I.T.), Italian Federation Department's Operators and Addiction Services (FederSerD), Italian Prison Medicine and Healthcare Society (S.I.M.S.Pe.). The considered population groups, having a high prevalence HBV and HCV infections, require specific interventions. In this context, the expression "special population" refers to specific vulnerable groups at risk of social exclusion, such as migrants, prison inmates, and intravenous drug users. When dealing with special population groups, social, environmental and clinical factors should be considered when selecting candidates for therapy as indicated by national and international guidelines., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The management of vitamin K antagonists (VKAs) associated coagulopathy is a cornerstone of pre-endoscopic assessment of anticoagulated patients presenting with acute gastrointestinal bleeding., Aims: To evaluate physician attitudes in the management of VKAs-associated coagulopathy in patients presenting with gastrointestinal bleeding and to assess their compliance to current practice guidelines., Design: Cross sectional physician web-based survey amongst regional members of three Italian Gastroenterological Societies (AIGO, SIED, SIGE) practicing in academic medical centres or community hospitals. Physicians were asked to provide management preferences in four hypothetical case-scenarios describing patients with warfarin-associated coagulopathy presenting with gastrointestinal bleeding of varying severity., Results: A total of 105 out of 238 (48%) members responded; mean age±SD: 46.3±9.8 years, 68% male. The adherence to practice guidelines for the reversal of warfarin-induced anticoagulation ranged from 24% to 86% and it was not dependent on age, years and type of specialisation, hospital setting and active performance of "on call" emergency endoscopy or not., Conclusions: There is a considerable variability amongst physicians in the management of gastrointestinal bleeding patients with VKAs-associated coagulopathy and a poor compliance to practice guidelines. These data indicate that better education is needed in this area., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Transient elastography (TE) has gained popularity for the non-invasive assessment of severity of chronic viral hepatitis, but a comprehensive evaluation of the factors that might account for discrepancy in diagnostic accuracy between TE and the standard of care liver biopsy (LB) is still needed., Methods: Patients with chronic hepatitis-B (HBV, n=104) or -C (HCV, n=453) underwent percutaneous LB concomitantly with TE (FibroScan®; Echosens, Paris, France). Liver cell necroinflammatory activity (A) and fibrosis (F) were assessed by METAVIR. Perisinusoidal fibrosis was rated with a 0-3 score. Determinants of TE results were investigated by a linear regression model whereas discordance between TE and LB results was assessed by logistic regression., Results: Fibrosis (p<0.0001) and liver cell necroinflammatory activity (p<0.0001) were independently associated with TE results in both HBV and HCV patients, whereas steatosis (p<0.0001) was independently associated with TE in HCV only. Fibrosis overestimation was predicted by severe/moderate necroinflammatory activity in HBV and by older age (41-60 or>60years vs.<40), >2 UNL AST and>2 UNL GGT, as well as severe/moderate necroinflammatory activity and severe/moderate steatosis in HCV. In the latter patients, however, moderate/severe necroinflammatory activity and steatosis were the only independent predictors of fibrosis overestimation., Conclusions: Fibrosis and necroinflammatory activity are the main determinants of TE in chronic viral hepatitis. Since TE staging of fibrosis is influenced by necroinflammatory activity and steatosis, a diagnostic LB is deemed necessary for a reliable intra-patient TE monitoring of the course of viral hepatitis., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: At presentation, gastroenteropancreatic neuroendocrine tumours (GEP NETs) frequently show prognostically negative hepatic involvement. The aim of this study was to characterise hepatic metastases of GEP NETs as revealed by contrast-enhanced ultrasonography (CEUS), which allows the fine definition of the microvascular system, and to correlate these findings to the biological behaviour of the tumour., Methods: Eighteen out of 62 GEP NET patients examined between January 2007 and September 2008 had histologically proven hepatic metastases from primary ileal (#6), gastric (#1) or rectal (#1) carcinoids, pancreatic tumours (#7), or primary duodenal (#2) or occult gastrinomas (#1), and all underwent low mechanical index real-time CEUS with SonoVue injection., Results: Strong early enhancement in the arterial phase was observed in 15 cases (83%), and a rapid wash-out in the portal venous phase in 14 (78%). In the late venous phase, the lesions were hypoechoic in 12 cases (67%), isoechoic in five (28%), and hyperechoic in one (0.05%). The time of arterial enhancement correlated with the Ki-67 proliferative index (r(s)=0.516; p=0.028)., Conclusions: Most of the neuroendocrine liver metastases showed increased arterial enhancement at CEUS, a behaviour that is similar to that of hepatocellular carcinomas and the opposite of that of other metastases. CEUS can be a useful diagnostic means of characterising such metastases., (Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The mechanisms by which elevated glucocorticoids contribute to decreased body mass via angiotensin II (Ang II) infusion are not completely described. This study addressed the hypothesis that chronic Ang II infusion suppresses hepatic growth hormone receptor (GHr) and IGF1 expressions via an Ang II receptor (AT1)-mediated pathway associated with elevated glucocorticoids. Sprague-Dawley rats were assigned to three groups: 1) Control, 2) Ang II-infused (80 ng/min x 28d) and 3) Ang II+angiotensin receptor blocker (ARB; 10 mg losartan/kg/d x 21d). After 28d, Ang II decreased body mass by 14% (407+/-8 vs 350+/-17 g) and hepatic AT1a, GHr, and IGF1 mRNA expressions by 45%, 44%, and 44%, respectively. ARB treatment completely prevented the loss in body mass (409+/-9 g) and AT1a and GHr expressions and partially recovered the loss of hepatic IGF1. Ang II increased plasma corticosterone (B) 3-fold (173+/-28 vs 555+/-42 ng/mL) and ARB treatment prevented the response (150+/-47 ng/mL). Food consumption did not change suggesting that the decrease in body mass resulted from the catabolic actions of the Ang II-induced increase in systemic B and not from reduced caloric intake. The prevention by ARB treatment of the Ang II-induced decrease in body mass and downregulation of AT1a, GHr and IGF1 coinciding with suppression of plasma B suggests that the Ang II-induced decrease in body mass is AT1 receptor mediated in conjunction with elevated B. These data suggest that alleviating the Ang II-induced cachexia requires targeting AT1 and suppressing glucocorticoid secretion., (Copyright 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.)

Background: Anastomotic biliary stricture represents one of the possible factors leading to liver dysfunction after transplantation., Purpose: Our aims were to evaluate the role of endoscopic retrograde cholangio-pancreatography and a short-term stenting (stent-trial) in assessment of the clinical relevance of the biliary stricture., Materials and Methods: Thirty transplanted patients for HCV (n=17) or non-HCV (n=13)-related cirrhosis (27M, median age 53 yr, range 24-67 yr) who developed persistently abnormal liver function tests and presented with an anastomotic biliary stricture suggested by non-invasive cholangiography, underwent endoscopic retrograde cholangio-pancreatography. If the stricture was confirmed, dilation was performed and a plastic stent was placed. Clinical and biochemical evaluation was done one and two months later. Resolution of symptoms and normalization or > 50% reduction of at least one liver function test were needed to consider the stricture as clinically relevant. Patients were followed up for a median of 19 months., Results: Endoscopic retrograde cholangio-pancreatography was successful in 29 patients and confirmed the anastomotic biliary stricture in 19 (66%); 14 patients underwent endoscopic dilation and stenting and five patients underwent surgery. The stent-trial suggested the stricture to be clinically relevant in 7 of 14 patients, confirmed by prolonged stenting and follow-up. A trend towards a higher likelihood of a clinically relevant stricture was observed in HCV-negative compared to HCV-positive patients (5 of 7, 71% vs 2 of 7, 29% , respectively; p=0.1)., Conclusions: Our data suggest that endoscopic retrograde cholangio-pancreatography is a valuable tool to evaluate the clinical relevance of an anastomotic stricture, when coupled with a short-term stent-trial.

A fusion gene, echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. We also analyzed ALK protein levels in paraffin samples from 662 NSCLC specimens, including the 120 cases investigated in the molecular studies. EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in non-cancerous lung tissues taken far from the tumor. Notably, no transcripts were detected in matching tumor samples from these patients. Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.

Background: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success., Aim: We evaluated plasma chromogranin A (CgA) as a marker of HCC., Patients: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls., Methods: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy)., Results: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3)., Conclusions: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.

Background/aims: Biochemical tests and ultrasonography (US) are useful in the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C (CH-C); however histology remains the reference standard. This multicenter, cross-sectional cohort study evaluated the accuracy of APRI (AST-to-platelet-ratio-index) and liver surface ultrasound nodularity (LSN), singularly and sequentially combined in an algorithm, in diagnosing advanced fibrosis (i.e. METAVIR F3,F4), to derive a prediction rule to confirm or exclude F3,F4., Methods: Four hundred and thirty consecutive CH-C patients with elevated ALT, grouped into a first cohort (training set), and an internal and an external validation cohort, were studied. APRI and LSN were compared to liver biopsy and sequentially combined in order to obtain a predictive rule for advanced fibrosis METAVIR F3,F4., Results: LSN was negative and APRI < or = 1 in 185/430 patients, whereas LSN was positive and APRI>2 in 46/430 cases, with a 94% diagnostic accuracy for presence/absence of F3, F4, respectively. In a further 60/430 patients, F3,F4 was detected with an accuracy of 83%. In the remaining cases no classification was possible., Conclusions: An algorithm based on APRI and LSN confirms or excludes F3,F4 in 54% of CH-C patients with elevated ALT and suggests a highly probable diagnosis in a further one-sixth of patients, thus rendering liver biopsy unnecessary in these patients.

Background: Twenty-four hours oesophageal pH monitoring is considered the reference-standard for the diagnosis of gastro-oesophageal reflux disease, but it is limited by catheter discomfort and limitations of daily habits., Aim: We evaluated tolerability and impact on food intake and daily activities of catheter-based compared to wireless pH monitoring., Patients: One-hundred and thirty-three consecutive patients with suspected gastro-oesophageal reflux disease were enrolled., Methods: Seventy-eight patients (36 M, 53+/-2 years) underwent the 24 h catheter-based and 55 patients (25 M, 44+/-3 years) the 48 h wireless pH monitoring. Discomfort at placement and during the test was evaluated by 100 mm visual analogue scales. Limitations of food intake and of daily activities were evaluated by standardized questionnaires (score 0 to 3)., Results: Discomfort (mean+/-standard error of the mean) at placement and during the test was 32+/-3 versus 29+/-4 (p=ns) and 37+/-3 versus 22+/-3 (p<0.001) for the catheter-based versus wireless techniques. Limitation of food intake and of daily activities (mean+/-standard error of the mean) were 0.9+/-0.1 versus 0.4+/-0.1 (p<0.05) and 1.2+/-0.1 versus 0.2+/-0.1 (p<0.0001), respectively., Conclusions: The wireless pH monitoring is better tolerated and has minor impact on daily habits compared to the traditional technique. Whether this translates into better diagnostic accuracy remains to be evaluated.

Background and Aims: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis., Materials and Methods: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance., Results: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05)., Conclusion: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

A 30-year-old man was referred because of a short lasting history of severe epigastric pain and early satiety, with remarkable weight loss. Physical examination was fully consistent with secondary syphilis and upper GI tract endoscopy revealed multiple gastric mucopurulent erosions and several nodular lesions ranging from 2 to 3 cm in diameter, with central crater, abruptly ending at the pyloric level. Appropriate antibiotic treatment obtained a dramatic improvement and complete reversal of cutaneous and gastric lesions.