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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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Percutaneous endoscopic gastrostomy is the preferred option for providing enteral nutrition, allowing for an improvement in survival and quality of life., Aim: To evaluate risk factors for early and delayed mortality after gastrostomy placement., Methods: A single-center retrospective analysis of a prospectively-collected database including all patients undergoing gastrostomy placement for enteral nutrition was performed. Two operators performed all the procedures according to the most recent guidelines., Results: Analysis included data on 438 patients [178 male; 80.5 (72-86) year-old]. Indications for PEG were stroke (34.0%), dementia (31.3%), neurodegenerative disorders (18.5%), coma (9.1%) and cancer (7.1%). No periprocedural adverse events was observed. Mean survival was 14.6±3.4months; 1-month and 3-month mortality rates were 4.0% and 8.1%, respectively. Severe hypernatremia (≥150mmol/L) was independently related to 1-month mortality (odds ratio 25.4; P<0.0001), while C-reactive protein level>4.3mg/dL was independently related to 3-month mortality (odds ratio 5.3; P=0.003). Kaplan-Meier and Cox-regression analysis identified male gender (hazard ratio 2.32; P=0.0002), severe hypernatremia (hazard ratio 4.3; P<0.0001), C-reactive protein>4.3mg/dL (hazard ratio 3.5; P=0.0014), leukocytosis (hazard ratio 1.97; P=0.0036) and presence of underlying malignancy (hazard ratio 2.4; P=0.0013) as independent risk factors for long-term mortality., Discussion: Presence of severe hypernatremia and increased C-reactive protein levels were strongly correlated with early and delayed mortality in our population. Studies are necessary to understand whether correcting underlying dehydration and inflammation further improves patients' outcomes., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Incidental pancreatic cysts (PCs) are frequently encountered in the general population often in asymptomatic patients who undergo imaging tests to investigate unrelated conditions. The detection of a PC poses a significant clinical dilemma, as the differential diagnosis is quite broad ranging from benign to malignant conditions. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) has been reported to be an accurate tool in the differential diagnosis; however, its sensitivity is suboptimal and false negative results do occur. Contrast harmonic EUS (CH-EUS) was demonstrated to be a useful tool to investigate pancreatic solid lesions to differentiate between benign and malignant ones. In the setting of PCs, CH-EUS could help identify areas of malignant growth inside the cystic cavities. Several studies have reported promising results showing malignant areas in PCs as hyperenhanced lesions. Confirmation of malignancy can then be obtained by FNA, which should be precisely targeted according to the findings of the contrast harmonic study.

It is well established that endoscopic ultrasound (EUS) is fundamental in the characterization of many diseases concerning different organs, i.e. pancreaticobiliary diseases, gastrointestinal pathologic conditions, and lymph nodes of unknown origin. It is also well known that many factors can hamper the accuracy of EUS, i.e. biliary stents, chronic pancreatitis, poor operator's expertise. These factors can also lead to suboptimal accuracy when cytological confirmation through EUS-fine needle aspiration (EUS-FNA) is indicated. In recent years, new technological tools have rapidly increased their clinical impact improving the diagnostic power of EUS and EUS-FNA. Among these new tools, the most investigated and useful ones are represented by contrast harmonic-EUS (CH-EUS) and EUS-elastography (EUS-E). The purpose of this paper is to provide, through a review of the literature, an update of the applications of CH-EUS and EUS-E in the routine clinical practice in pancreatic diseases. We discussed the first reports and applications of these techniques in our previous review published in Minerva Medica. The applications of CH-EUS and EUS-E to the study of pancreatic diseases appear feasible and safe. The use of both techniques is very simple and does not require any relevant additional workload for the endoscopic personnel. CH-EUS is now considered an important and accurate tool in the diagnosis of solid pancreatic masses and in the differential diagnosis of pancreatic cystic lesions. CH-EUS targeted FNA is an active field of research. However the available studies show that CH-EUS increases FNA accuracy by a little extent, without statistical significance; moreover, CH-EUS FNA showed a trend toward being more efficient vs. simple EUS FNA (less needle passes and more abundance in cytological material) but this trend did not reach statistical significance. On the other hand, the clinical impact of EUS-E in terms of differential diagnosis of pancreatic masses is still under investigation. Chronic pancreatitis evaluation represents the most recent field of application of EUS-E that shows promising results.

Introduction: Endoscopic necrosectomy is now becoming common worldwide as a minimally-invasive treatment alternative to surgical necrosectomy. The aims of this systematic review are to record the entire body of the literature accumulated over the past 15 years on endoscopic necrosectomy techniques and to compare the outcomes of endoscopic versus non-endoscopic techniques., Evidence Acquisition: All relevant articles were extracted up to December 2015 based on the results of searches in PubMed, Scopus and Google Scholar., Evidence Synthesis: A total of 46 pertinent articles were finally included for the purpose of this systematic review. Most of the studies in our review included small numbers of patients, were retrospective and had low/moderate overall levels of evidence. The mean technical and clinical success rates reported were 99% and 89%, respectively, the mean overall complication rate was 22% and the mean overall mortality rate was 5%. The most common complications were bleeding, which occurred in 11% of patients, perforations/pneumoperitoneum which occurred in 3%, and air embolism in 0.4% of patients. The access to the cavity was created by direct endoscopic puncture in 205 patients, while endoscopic ultrasound guidance was used in 733, with no difference in technical success (99% vs. 99%), clinical success (87% vs. 89%), complications (32% vs. 21%) and mortality (7% vs. 5%) rates. Compared to the percutaneous and surgical therapies, the endoscopic techniques exhibited higher success rates and lower morbidity and mortality rates., Conclusions: Endoscopic necrosectomy is becoming the standard of care for the treatment of pancreatic necrotic collections.

Background: Endoscopic ultrasound (EUS) is accurate for the diagnosis of choledocholithiasis; however, data are lacking regarding the prediction of stone number and size., Aims: To evaluate the concordance between EUS and endoscopic retrograde cholangiopancreatography (ERCP) in stone number and size assessment., Methods: We performed a retrospective analysis of consecutive patients undergoing ERCP due to detection of choledocholithiasis by EUS. Concordance between EUS and ERCP was defined as difference in stone diameter <30% and perfect match in stone number., Results: Among 116 patients, 25% had sludge, 37.9% had single and 37.1% had multiple stones. Overall concordance was 62.9%. Sludge was correctly assessed in 85.7%, single stone in 81.3% and multiple stones in 45.1% (P=0.0001). EUS was accurate in 78.8% of patients who underwent both procedures in the same session, but only in 61.9% in those who underwent ERCP within 1 week. Multivariate analysis identified the single-session approach (odds ratio 2.894; P=0.035) and multiple stones (odds ratio 0.244; P=0.001) as independent predictors of concordance., Conclusions: Concordance between EUS and ERCP was correlated to the single session approach and inversely correlated to the presence of multiple stones. EUS may predict potentially difficult ERCP allowing to plan the best treatment strategy., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

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.

The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound (EUS)-guided treatments. These include EUS-guided drainage of pancreatic fluid collections, EUS-guided necrosectomy, EUS-guided cholangiography and biliary drainage, EUS-guided pancreatography and pancreatic duct drainage, EUS-guided gallbladder drainage, EUS-guided drainage of abdominal and pelvic fluid collections, EUS-guided celiac plexus block and celiac plexus neurolysis, EUS-guided pancreatic cyst ablation, EUS-guided vascular interventions, EUS-guided delivery of antitumoral agents and EUS-guided fiducial placement and brachytherapy. However these procedures are technically challenging and require expertise in both EUS and interventional endoscopy, such as endoscopic retrograde cholangiopancreatography and gastrointestinal stenting. We undertook a systematic review to record the entire body of literature accumulated over the past 2 decades on EUS-guided interventions with the objective of performing a critical appraisal of published articles, based on the classification of studies according to levels of evidence, in order to assess the scientific progress made in this field.

Unlabelled: 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., (© 2013 by the American Association for the Study of Liver Diseases.)

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.

Intrahepatic cholestasis of pregnancy is the most common liver disease occurring in the second half of pregnancy, characterized by pruritus and elevated serum bile acids often coupled to abnormal liver tests. Maternal prognosis is favourable with a complete symptom resolution after delivery, while preterm deliveries, fetal respiratory distress and stillbirths may occur. The goal of the pharmacological treatment of the disease is to improve maternal symptoms and biochemical alterations and, most importantly, to reduce fetal adverse events.The present manuscript will review the current knowledge on the pharmacological treatment of intrahepatic cholestasis of pregnancy.