Endoscopic ultrasound (EUS)-guided interventions on the liver such as diffuse biopsy and portal pressure gradient measurement are emerging as potential alternatives to percutaneous procedures. The purpose of this editorial was to address all the indications that could potentially make an EUS-guided approach a possible alternative to the percutaneous procedures with respect to the proce-dures that could join the EUS examination such as upper endoscopy for gastro-esophageal varices, pancreaticobiliary investigation with EUS, and other potential advantages in terms of patient safety. The issue of a holistic gastroenterologist approach was also discussed along with the potential for developing clinical research.

Background and study aims The endoscopic report has a key role in quality improvement for gastrointestinal endoscopy. High quality standards have been set by the endoscopic societies in this field. Unlike other digestive endoscopy procedures, the quality of reporting in endoscopic ultrasound (EUS) has not been thoroughly evaluated and a reference standard is lacking. Methods We performed an international online survey concerning the attitudes of endosonographers towards EUS reports in order to understand the needs for standardization and quality improvement. Endosonographers from different countries and institutional setting, with varying case volume and experience were invited to take part to complete a structured questionnaire. Results We collected replies from 171 endosonographers. Overall analysis of results according to case volume, experience and working environment of respondents (academic, public hospital, private) are provided. In brief, everyone agreed on the need for standardization of EUS reporting. The use of minimal standard terminology and a structured tree with mandatory items was considered of primary importance. Image documentation was also deemed fundamental in complementing EUS reports both for patient documentation and research purposes. A strong demand for connection and consultation among endosonographers for clinical and training needs was also found. In this respect, a formal expert consultation network was advocated in order to improve the quality of reporting in EUS. Conclusions Our survey showed a strong agreement among endosonographers who expressed the need for a standardization in order to improve the report and, as a consequence, the quality of EUS.

Endoscopic ultrasound (EUS)-guided gastrointestinal anastomosis with a lumenapposing metal stent (LAMS) is an effective alternative to intraluminal stenting for upper gastrointestinal obstruction [1, 2]. Recently, EUS-guided jejuno-jejunal anastomosis (EUS-JJA) has been reported for adhesive obstruction after gastric bypass and afferent loop syndrome [3–5]. A 75-year-old man presented with progressive epigastric pain and weight loss due to advanced malignancy after a previous total gastrectomy. Peritoneal recurrence had been diagnosed 2 years after the gastrectomy, and he had received chemotherapy, achieving stable disease for more than 3 years. On this presentation, as celiac trunk infiltration had been found on a recent computed tomography (CT) scan, it was agreed after multidisciplinary discussion that EUS-guided celiac plexus neurolysis should be performed; however, this failed to provide pain relief. At the time of EUS, a tight jejunal stenosis was observed 8 cm below the esophagojejunal anastomosis (▶Fig. 1). Given the persistence of symptoms, together with vomiting, the patient underwent EUS-JJA 2 weeks later, after receiving a detailed explanation of the off-label use of the LAMS. A nasobiliary tube was advanced through the stricture and used to fill the jejunal limbs with a methylene blue–saline solution to look for an adequate operative window. A 19-gauge needle was then inserted into the target loop to check for methylene blue aspiration and to inject contrast. A 20×10-mm electrocautery-enhanced LAMS (HotAXIOS; Boston Scientific, Natick, Massachusetts, USA) was inserted “free-hand” and then dilated up to 18mm (▶Fig. 2 and ▶Fig. 3 a, b). A pediatric gastroscope was finally advanced through the LAMS to assess the post-anastomotic jejunal limb (▶Fig. 3 c) On the first postoperative day, a contrast study showed restoration of bowel transit (▶Video 1) and oral feeding was resumed. The patient tolerated the procedure well and returned home 5 days later. He maintained adequate oral feeding and regained 2kg of weight during the following 2 weeks, allowing chemotherapy to be restarted. Interestingly, he experienced significant improvement in pain control too. EUS-JJA seems an effective treatment for malignant jejunal outlet obstruction.

Background and study aims Carbon dioxide (CO2) is being increasingly used for insufflation during endoscopy for safety and better tolerance. The role of CO2 during endoscopic ultrasonography (EUS) has not been studied yet. Our main aim was to compare the effects of CO2 vs. air insufflation on abdominal discomfort in patients undergoing EUS. Our secondary outcomes were to ascertain the effects of CO2 insufflation on image quality/visual artifacts and on the amount of sedation. Patients and methods This was a prospective, controlled, single-blind, observational study. Abdominal discomfort was assessed before diagnostic EUS, and 1 and 3 hours post-procedure and recorded as a visual analogue scale. Image quality was also recorded as a 4-point scale from optimal to poor at four different scanning sites (esophagus, stomach, duodenal bulb and second portion). Results A total of 198 patients were enrolled. We observed that CO2 resulted in less abdominal discomfort than air insufflation that was statistically significant at 3 hours (P= 0.048) but not at 1 hour after EUS (P=0.112), probably due to the ongoing effects of sedation at the latter stage. On the other hand, no differences were found in the dose of sedation administered in the two groups. Image quality was significantly better in the CO2 group compared to the air group at all four different scanning sites (P<0.01). Similarly, CO2 correlated with less visual artifacts and need of suction (P<0.01). Conclusions Similarly to previous findings with other endoscopic procedures, EUS was associated with improved scores for abdominal discomfort with CO2 rather than air insufflation. Moreover, overall EUS image quality was improved using CO2 insufflation. Future studies are warranted to ascertain whether CO2 insufflation should be regarded as the standard of care for diagnostic EUS.

Background The differential diagnosis between benign and malignant lymph nodes (LNs) is crucial for patient management and clinical outcome. The use of contrast-enhanced endoscopic ultrasound (EUS) has been evaluated in several studies with diverse results. The aim of this meta-analysis was to evaluate the pooled diagnostic accuracy of contrast-enhanced EUS (CE-EUS) and contrast-enhanced harmonic EUS (CH-EUS) in this setting. Methods A systematic electronic search was performed, including all original papers dealing with assessment of the nature of the LNs using CE-EUS or CH-EUS. A meta-analysis was performed to obtain pooled sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. The Summary Receiver Operating Characteristic (ROC) Curve method was used to calculate the area under the curve. Statistical analysis was carried out using Meta-Disc V.1.4, Stata V.12.0 and Review Manager V.5.2. Results Among 210 pertinent studies, four (336 patients) were included in the analysis. The pooled sensitivity was 82.1% (75.1-87.7%) and pooled specificity was 90.7% (85.9-94.3%) with significant heterogeneity found in sensitivity; the positive-likelihood ratio (LR) was 7.77 (5.09-11.85) and the negative-LR was 0.15 (0.05-0.46); the pooled diagnostic odds ratio (DOR) was 54 (15-190). Subgroup analysis including studies performed using CH-EUS (two studies, 177 LNs) showed a pooled sensitivity of 87.7% (77.0-93.9%) and a pooled specificity of 91.8% (84.5%-96.4%) with no significant heterogeneity; the pooled positive-LR was 9.51 (4.95-18.28) and the pooled negative-LR was 0.14 (0.06-0.35); pooled DOR was 68.42 (15.5-301.4). Conclusions From these data, CE-EUS is not recommended due to inadequate sensitivity. On the other hand, CH-EUS studies showed optimal accuracy (pooled sensitivity 87.7% and specificity 91.8%), comparable to elastography and even EUS-guided fine needle aspiration (EUS-FNA), suggesting a role in the diagnostic algorithm.

BACKGROUND:Endoscopic ultrasound (EUS) has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice.METHOD:We conducted a systematic review of the available English-language articles.OBJECTIVE:The purpose of this review is to summarize the relevant applications of operative EUS.RESULTS:More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. The main indications of operative EUS, both diagnostic and therapeutic, are related to its ability to combine ultrasound imaging and safe and effective needle insertion into lesions originating from the gut wall and from organs nearby. In addition, technologic advancements of echoendoscopes with a therapeutic working-channel have allowed to perform several EUS-guided interventions, i.e. celiac plexus neurolysis, drainage of fluid collections, drainage of dilated biliary and pancreatic ducts, and vascular interventions.

Background: Endoscopic Ultrasound has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. Method: We conducted a systematic review of the available English-language articles. Objective: The purpose of this review is to summarize all the relevant indications to endoscopic ultrasound and analyze its relevant data in terms of accuracy and clinical outcomes. Results: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. Staging indications include gastroesophageal and rectal cancers. Diagnostic, staging and therapeutic indications include diseases of the pancreaticobiliary area. Finally, differential diagnosis of submucosal tumors represents another important indication to this technique.

Background & Aims: Indocyanine green retention test (ICG-r15) is a non-invasive marker of functional hepatic reserve. Among patients with compensated cirrhosis, ICG-r15 correlates to the degree of portal hypertension (PH); however, its prognostic relationship with the occurrence of decompensation events still requires clarification. Methods: ICG-r15 was prospectively measured in 154 patients with compensated cirrhosis. Patients with hepatocellular carcinoma (HCC), Child-Pugh B-C, MELD> 15, bilirubin > 2 mg/dl, INR > 1.5 or portal vein thrombosis were excluded. All patients underwent laboratory tests, upper endoscopy and hepatic venous pressure gradient (HVPG). Decompensation, development of HCC, liver transplant and death were recorded and analysed through competing-risk analysis. Results: The study group was composed of 134 patients who were followed for a median of 39 months. During follow-up, 46 patients (34.3%) developed liver decompensation. Hepatocellular carcinoma occurred in 18 patients and two patients died from non-liver-related causes. The 1-, 2-and 3-year cumulative incidences of decompensation were 9.7%, 28.4% and 33.4% respectively. Patients with ICG-r15 < 10% did not experience any decompensation events during follow-up, while the 3-year cumulative incidence of decompensation of patients with ICG-r15 between 10% and 22.9% was 29.2% and that of patients with ICG-r15 >= 23% was 70.0% (P < 0.001). ICG-r15 gave the lowest pseudo-log-likelihood value, in comparison to oesophageal varices present, MELD, low platelet count and HVPG. Conclusions: ICG-r15 appears to be strictly related to liver decompensation, longitudinally confirming the preliminary findings of its correlation with PH among patients with compensated cirrhosis, and can be used for patient prognostication.

BACKGROUND:Fitz-Hugh-Curtis syndrome is a rare extra-pelvic complication of genital infection involving the perihepatic capsule. Most cases have been described in women in association with pelvic inflammatory disease; in rare cases it has been reported in men. Because the main symptom is acute abdominal pain, and laboratory and imaging findings are frequently nonspecific, the differential diagnosis, considering other gastrointestinal or renal diseases, can be difficult in the early stage of the syndrome, leading to frequent misdiagnosis and mismanagement.CASE REPORT:We report a case of Fitz-Hugh-Curtis syndrome in a 26-year-old man who first presented to the emergency department with acute abdominal pain, vomiting, and fever. Diagnosis was possible on the basis of clinical signs of orchiepididymitis, abnormal ultrasound findings, and specialist consultation with the Sexually Transmitted Infection Clinic. An acute gonoccocal infection was revealed, which was complicated by a collection of free perihepatic fluid and a subcapsular hypoechoic focal lesion. Prompt antibiotic therapy was established, with complete resolution of the symptoms within a few days. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Awareness of the clinical presentation, imaging, and laboratory findings during the acute phase of Fitz-Hugh-Curtis syndrome could help emergency physicians to make an early diagnosis and to correctly manage such patients. Improved diagnostic skills could prevent chronic complications that are especially a risk in the case of delayed or minor genitourinary symptoms.

The occurrence of de novo hepatocellular carcinoma after liver transplantation is a rare event with only few cases reported in the literature. In a post liver transplantation setting distinguishing between a de novo hepatocellular carcinoma from recurrence should be tested with molecular analysis such as fluorescent in situ hybridization (for sex chromosomes) or microsatellite analysis. Nevertheless, a certain degree of epithelial chimerism between recipient and donor tissues could be responsible for the development of de novo hepatocellular carcinoma of recipient origin. We report two cases of de novo hepatocellular carcinoma after liver transplantation. The first one occurred in a patient receiving transplantation for hepatitis C related cirrhosis and hepatocellular carcinoma. A de novo hepatocellular carcinoma developed five years after transplantation and microsatellite analysis revealed the donor origin of the neoplasia. The second one occurred in a patient who received transplantation for secondary sclerosing cholangitis. Hepatocellular carcinoma was found six years after transplantation. Both microsatellite analysis and fluorescent in situ hybridization revealed the recipient origin of the tumor, potentially due to tissue chimerism.

Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation.

*Microbiology Unit, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, University of Bologna, St Orsola Hospital, Bologna, Italy, †Dermatology Unit, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, University of Bologna, St Orsola Hospital, Bologna, Italy, and ‡Gastroenterology Unit, Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, St Orsola Hospital, Bologna, Italy Reprint Address: Paola Nardini, MD, Microbiology Unit, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, University of Bologna, St Orsola Hospital, Via Massarenti, 9, 40138, Bologna, Italy

Noninvasive markers would be useful for the assessment of portal hypertension (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study was to evaluate the performance of the indocyanine green (ICG) retention test as a noninvasive marker of PH and EV, measured against the gold standards (hepatic venous pressure gradient [HVPG] measurement and upper endoscopy). We prospectively enrolled patients with compensated cirrhosis referral to our unit. All patients underwent laboratory tests, abdominal ultrasound, upper gastrointestinal endoscopy, HVPG measurement, and the ICG 15‐minute retention (ICG‐r15) test. We evaluated the sensitivity and specificity of the ICG retention test and other noninvasive tools for the diagnosis of PH and EV. Ninety‐six consecutive Child‐Pugh A patients (67 male and 29 female; 60.3 ± 11.8 years of age) were enrolled. Seventy‐four patients had clinically significant portal hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG‐r15 and Lok index were independently related to the presence of both CSPH and SPH, whereas ICG‐r15 and INR were related to EV. ICG‐r15 values (<6.7% and <6.9%, respectively) were able to rule out the presence of CSPH and SPH (LR− 0.15 and 0.14); ICG‐r15 <10% provided a 97.8% sensitivity (LR− 0.042) for the exclusion of EV and a 100% sensitivity (LR− 0.0) for large EV. Conclusion: The ICG‐r15 test is an effective tool for assessment of PH in patients with compensated cirrhosis. Although this would not replace endoscopy, the ICG‐r15 appears able to identify patients with advanced liver disease in which endoscopy is mandatory as well as rule out the presence of EV in patients with compensated cirrhosis. (Hepatology 2014;59:643–650)

Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes and coronary stent implantation. Patients with CV co-morbidities, receiving antiplatelet agents because of their usefulness in primary or secondary cardiovascular prevention, present a significantly increased GI risk; therefore in those patients gastroprotective agents are useful to reduce this risk. Laboratory studies suggested a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered; those data were corroborated from large retrospective studies. Strong evidence from RCTs and systematic review evaluating the clinical interaction between PPI and clopidogrel failed to demonstrate difference in cardiovascular outcomes, confirming a significant reduction in gastrointestinal bleeding in PPI users. To date, the available evidences do not support the warning that PPI prescription could worsen clinical outcome of patients receiving clopidogrel.

AIM:To evaluate the effect of long-term treatment with leukocyte natural α-interferon (ln-α-IFN) plus ribavirin (RBV).METHODS:Forty-six patients with hepatitis C virus (HCV) recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo; then, patients with good tolerability (n = 30) were switched to daily IFN administration, while the remaining were treated with the same schedule. Patients have been treated for 12 mo after viral clearance while non-responders (NR) entered in the long-term treatment group. Liver biopsies were planned at baseline, 1 year after sustained virological response (SVR) and at 36 mo after start of therapy in NR. MedCalc software package was used for statistical analysis.RESULTS:About 16.7% of genotype 1-4 and 70% of genotype 2-3 patients achieved SVR. Nine patients withdrew therapy because of non-tolerance or non-compliance. A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated; 100% of patients with SVR achieved a histological response (fibrosis stabilization or improvement) with a significant reduction in mean staging value (from 2.1 to 1.0; P = 0.0031); histological response was observed in 84% of long-term treated patients compared to 57% of drop-out. Six patients died during the entire study period (follow-up 40.6 ± 7.7 mo); of them, 5 presented with severe HCV recurrence on enrollment. Diabetes (OR = 0.38, 95%CI: 0.08-0.59, P = 0.01), leukopenia (OR = 0.54, 95%CI: 0.03-0.57, P = 0.03) and severe HCV recurrence (OR = 0.51, 95%CI: 0.25-0.69, P = 0.0003) were variables associated to survival. Long-term treatment was well tolerated; no patients developed rejection or autoimmune disease.CONCLUSION:Long-term treatment improves histology in SVR patients and slows disease progression also in NR, leading to a reduction in liver decompensation, graft failure and liver-related death.

Abstract Background. The presence of refractory ascites is a common indication for transjugular intrahepatic portosystemic shunt (TIPS). Different models have been proposed for the prediction of survival after TIPS. The aim of this study was to evaluate the predictive factors associated with patients' survival after TIPS placement for refractory ascites. Methods. Data from all consecutive patients undergoing TIPS placement in our center for refractory ascites between February 2003 and January 2008 were prospectively recorded. Results. Seventy-three patients (52M/21F; 57 ± 10 years) met the inclusion criteria; mean follow-up was 17 ± 2 months. Mean MELD value, before TIPS placement, was 15.7 ± 5.3. TIPS placement led to an effective resolution of refractory ascites in 54% of patients (n = 40) with no significant increase in severe portosystemic encephalopathy. The 1-year survival rate observed was 65.7%, while the overall mortality was 23.3% (n = 17) with a mean survival of 17 ± 14 months. MELD score (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B = 0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1-year survival. ROC curves identified MELD ≥ 19 and HVPG ≥ 25 mmHg as the best cut-off points for the prediction of 1-year mortality. Conclusions. TIPS is an effective treatment for refractory ascites in cirrhotic patients, leading to an effective ascites control in more than half patients. Improvement in patients' selection criteria could lead to better outcome and survival after this procedure. Liver function (MELD), presence of active necroinflammation (AST), and portal hypertension (HVPG) are independent predictors of patients' outcome after TIPS.

Alisporivir (DEB025), a cyclosporin A derivative, is a new antiviral drug which targets host cell factors (cyclophilins) inhibiting viral replication without immunosuppressive effects. This drug potently inhibits cyclophilin-dependent HCV replication with an additive antiviral effect to standard-of-care (SoC) therapy for HCV. The administration of alisporivir in addition to SoC enhances activity against all HCV genotypes, with a good safety profile. Currently, two trials are ongoing: a Phase III and a Phase II trial assessing the efficacy of alisporivir plus SoC in genotype-1 treatment-naive patients and nonresponders or relapsers. Another Phase II study is examining the potential use of alisporivir for IFN-free treatment in HCV genotype 2 and 3 patients naive to treatment. In this review, we describe the unique characteristics of this cyclophilin inhibitor and benefit afforded by this drug in combination therapy with current and future HCV treatments.

Moreover, low-dose aspirin therapy induce a significant reduction in cardiovascular (CV) and cerebrovascular events and effectively lower the rate of deaths in patients with cardiovascular risk factors and previous CV events. On the other hand, adverse gastrointestinal events related to NSAIDs therapy occur in a little but significant amount of patients, resulting in an important morbidity and mortality; world mortality secondary to NSAIDs therapy has been estimated to be similar to that caused by HIV-related complications (Abraham et al., 2005; Laine et al., 2010). For example, in the US more than