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Objective: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS-RFA for pNENs., Methods: The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS-RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I 2 . Pooled estimates and the 95% confidence interval (CI) were calculated using a random-effect model., Results: Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9-99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1-92.8%). The pooled partial response was 11.4% (95% CI 6.2-18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7-97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0-26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2-2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported., Conclusion: Endoscopic ultrasound-guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: standard B-mode EUS assessment and EUS-guided tissue acquisition present sub-optimal diagnostic yield in the differential diagnosis of gastric submucosal tumors (SMTs)., Aims: to evaluate the performances of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) to differentiate gastric SMTs and predict malignancy risk of gastrointestinal stromal tumors (GIST)., Methods: a retrospective analysis was performed retrieving consecutive patients with gastric SMTs who underwent EUS between 2009 and 2014. Patients with available EUS video recordings and histological diagnosis were included. De-identified videos were presented to experts who made a diagnosis on B-mode EUS and CH-EUS., Results: fifty-four patients (29 female, 64-year-old) were included. Final diagnoses were 40 GISTs (8 high-grade), 9 leiomyomas, 5 rare SMTs. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the differential diagnosis of GIST were 95.0% vs. 85.0%, 57.1% for both techniques, and 85.2% vs. 77.8%, respectively. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the estimation of the malignancy GISTs risk were 62.5% vs. 100%, 83.3% vs. 82.1%, and 78.9% vs. 86.1%, respectively., Conclusions: CH-EUS showed better diagnostic performance than B-mode EUS in differentiating leiomyomas and risk stratification of GIST. When considering high-grade GISTs, the addition of CH-EUS allowed an improvement in diagnostic accuracy., Competing Interests: Declaration of Competing Interest The Authors declare no conflict of interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Aims: Pancreatic cystic neoplasms (PCNs) carry a considerable malignancy risk. Along with main duct dilation, the presence of enhanced mural nodules represents a significant risk factor for malignancy. Several articles assessed the role of contrast-enhanced EUS (CE-EUS) for the identification of malignant features in mural nodules. We evaluate the pooled diagnostic performance of CE-EUS for the identification of high-grade dysplasia or invasive carcinoma among mural nodules in PCNs., Methods: A systematic review (Medline, PubMed, EMBASE) and meta-analysis were conducted. Subgroup analysis was used to assess the usefulness of a dedicated contrast-harmonic (CH-EUS). The primary outcome was pooled sensitivity for identification of high-grade dysplasia or invasive carcinoma., Results: Ten studies (532 patients) were included. Pooled sensitivity of CE-EUS was 88.2% (95% confidence interval [CI], 82.7%-92.5%), specificity 79.1% (95% CI, 74.5%-83.3%), and diagnostic accuracy 89.6% (95% CI, 83.4%-95.8%). Eight studies (320 patients) were conducted using CH-EUS: pooled sensitivity increased to 97.0% (95% CI, 92.5%-99.2%), specificity to 90.4% (95% CI, 85.2%-94.2%), and diagnostic accuracy to 95.6% (95% CI, 92.6%-98.7%). At 42% disease prevalence (pretest probability), a positive CH-EUS increased the disease probability to 88%, whereas a negative test decreased the disease probability to 2%. The number needed to diagnose was 1.5 (95% CI, 1.7-1.3) for CE-EUS and just 1.2 (95% CI, 1.3-1.1) for CH-EUS., Conclusions: This study provided robust evidence on CE-EUS value for the characterization of mural nodules within PCNs. A dedicated contrast-harmonic mode, namely CH-EUS, provided an increased diagnostic yield in the identification and characterization of malignant mural nodules., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The Asian Federation of Societies for Ultrasound in Medicine and Biology aimed to provide information on techniques and indications for contrast-enhanced harmonic endoscopic ultrasound (CH-EUS), and to create statements including the level of recommendation. These statements are based on current scientific evidence reviewed by a Consensus Panel of 15 internationally renowned experts. The reliability of clinical questions was measured by agreement rates after voting. Six statements were made on techniques, including suitable contrast agents for CH-EUS, differences between contrast agents, setting of mechanical index, dual imaging and duration and phases for observation. Thirteen statements were made on indications, including pancreatic solid masses, pancreatic cancer staging, pancreatic cystic lesions and mural nodules, detection of subtle pancreatic lesions, gallbladder sludge and polyps, hepatic lesions, lymph nodes, subepithelial lesions, visceral vascular diseases, guidance of fine needle aspiration and evaluation for local therapy. These international expert consensus guidelines will assist endosonographers in conducting CH-EUS according to evidence-based information., Competing Interests: Conflict of interest disclosure Masayuki Kitano and Bertrand Napoléon received lecture fee from Olympus; Masatoshi Kudo serves as a consultant to Bristol-Myers Squibb and received lecture fee from Bristol-Myers Squibb; Anthony Y.B. Teoh is a consultant for Boston Scientific, Cook, Taewoong and Microtech Medical Corporations. The remaining authors declare that they have no conflicts of interests regarding the publication of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: None

Competing Interests: None

Background: Current imaging modalities are limited in their ability to distinguish pancreatic cancer (PC) from non-neoplastic pancreatic lesions. The diagnostic use of contrast-enhanced endoscopic ultrasonography (CE-EUS) has increased, and its utility has been reported. Recently, contrast-enhanced harmonic EUS (CH-EUS) was reported to facilitate imaging of parenchymal perfusion and microvessels in pancreatobiliary diseases, leading to a high diagnostic accuracy for PC. The present meta-analysis aims to investigate the usefulness of CH-EUS with enhancement pattern for PC diagnosis., Methods: A systematic meta-analysis of all potentially relevant articles identified in PubMed, the Cochrane library, and Medline was carried out. Fixed-effects or random-effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI)., Results: The study enrolled 887 patients from nine eligible studies. Pooled estimates of sensitivity and specificity were 93% (95% CI, 0.91-0.95) and 80% (95% CI, 0.75-0.85), respectively. Subgroup analyses were carried out on the main results after excluding two outliers. Area under summary receiver operating characteristics curve was 0.97. No publication bias was found using funnel plots. No significant relationship was found between the diagnostic odds ratios and the characteristics of the studies including continent and contrast agent., Conclusions: This meta-analysis showed that CH-EUS with qualitative analysis of enhancement pattern is useful for the diagnosis of PC, and has high sensitivity and accuracy, regardless of the type of contrast agent used. This modality may provide improved diagnostic accuracy for PC in clinical practice., (© 2018 Japan Gastroenterological Endoscopy Society.)

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

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 and Aim: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions., Methods: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images., Results: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87%, 71-88%, and 74-86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis., Conclusion: CH-EUS was useful for the evaluation of localized gallbladder lesions., (© 2017 Japan Gastroenterological Endoscopy Society.)

Background and Aim: The study aims to evaluate contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for the differential diagnosis of submucosal tumors (SMT) of the upper gastrointestinal tract., Methods: Between June 2008 and May 2015, 157 consecutive patients with submucosal lesions of the upper gastrointestinal tract were evaluated by CH-EUS. This was a single-center retrospective analysis of prospectively collected data in a registry. The data from 73 patients who later underwent surgical resection were analyzed in this study. Surgical specimens served as the final diagnoses. The two CH-EUS variables of blood flow (hyper-enhancement vs hypo-enhancement) and homogeneity of enhancement pattern were evaluated., Results: The final diagnoses were 58 gastrointestinal stromal tumors (GISTs) and 15 benign SMTs (two lipomas, five leiomyomas, five schwannomas, two glomus tumors, and one ectopic pancreas). On CH-EUS, 49 of 58 (84.5%) GISTs presented with hyper-enhancement, whereas 4 of 15 (26.7%) benign SMTs showed hyper-enhancement; 21 of 58 (36.2%) GISTs showed inhomogeneous contrast enhancement, while only 2 of 15 (13.3%) benign SMTs demonstrated inhomogeneous contrast enhancement. If hyper-enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 84.5%, 73.3%, and 82.2%, respectively. If inhomogeneous enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 36.2%, 86.7%, and 46.6%, respectively. In lesions of less than 2 cm, hyper-enhancement was a more sensitive indicator of GISTs than inhomogeneous enhancement., Conclusions: Hyper-enhancement and inhomogeneous enhancement were found to be a characteristic of GISTs. CH-EUS was useful for discrimination of benign SMTs from GISTs., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the literature to put its clinical outcomes in the appropriate perspective., Methods: We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines., Results: Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3)., Conclusions: The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

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.

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Objectives: To evaluate the potential role of contrast harmonic endoscopic ultrasound (CH-EUS) in the differential diagnosis of pancreatic cysts and detection of malignancy., Methods: Patients who underwent CH-EUS for evaluation of cyst wall, septae, and solid components of pancreatic cysts were included. The findings were compared to fine needle aspiration and surgery., Results: Seventy-six patients were included. Serous and mucinous cysts were both hyperenhanced (86% and 89%, respectively; P = ns), whereas pseudocysts were hypoenhanced in 90% of the cases (P = 0.000004 vs serous cysts and P = 0.000005 vs mucinous cysts). Patients showing hyperenhanced solid components were finally diagnosed with malignancy (2 malignant intraductal papillary mucinous neoplasms, 2 cystic neuroendocrine tumors), in contrast to the patients with nonenhanced solid components who resulted to have either benign cysts with internal mucus clots (n = 10) or pseudocysts with internal debris (n = 8)., Conclusions: CH-EUS allowed differentiation between pseudocysts and other pancreatic cysts but not mucinous versus serous cysts. Malignant vegetations inside pancreatic cystic lesions were clearly shown by CH-EUS as solid components with features of hyperenhancement, directing EUS-fine needle aspiration of potential neoplastic areas and avoiding puncture of debris and mucus plugs.

Endoscopic ultrasound is a very accurate imaging technique with a relevant clinical impact in the diagnosis and staging of various conditions such as pancreaticobiliary lesions, esophageal cancer, lung cancer, submucosal lesions and lymph nodes. Despite its increasing importance in everyday clinical routine, endoscopic ultrasound outcomes are still highly operator-dependent and tissue confirmation with fine needle aspiration is very often required for definitive differential diagnosis of tumors. Several techniques of image enhancement have been developed in recent years in the attempt to make the technique less operator-dependent. Among them the most important appear to be contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography. Contrast harmonic-endoscopic ultrasound is performed with a dedicated harmonic which displays the fine vascular network of both normal and pathological tissues after injection of an ultrasound contrast agent. Endoscopic ultrasound-elastography displays with different colors the differences in hardness between tissues, thus estimating elasticity in soft normal tissues which appear red and hard neoplastic tissues which appear blue. While contrast harmonic-endoscopic ultrasound has been introduced into clinical practice, endoscopic ultrasound-elastography mainly represents an investigational tool. The purpose of this paper was to review the mechanism of action and the clinical outcomes of contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography in pancreatic diseases. Both techniques show promising applications in the study of pancreatic tumors including differential diagnosis and providing guidance to fine needle aspiration.

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.

Objective: The differential diagnosis between primary pancreatic neoplasms versus pancreatic metastases (PM) is challenging. Endoscopic ultrasonography with fine-needle aspiration can be used to differentiate primary versus metastatic tumors although with a suboptimal accuracy. Recently, contrast harmonic EUS (CH-EUS) has been reported as an adjunct in the diagnosis of pancreatic neoplasms. We evaluated the potential role of CH-EUS in the differential diagnosis of PM., Methods: This study is a retrospective analysis of a prospectively maintained database. Of the 266 patients, 4.1% were diagnosed with PM. Endoscopic ultrasonography with fine-needle aspiration and/or surgical pathology represented our criterion standard., Results: The origins of PM were renal cancer (3 patients), colon cancer(2 patients), breast cancer (2 patients), ovarian cancer (1 patient), melanoma(1 patient), lymphoma (1 patient), and sarcoma (1 patient). All lesions appeared hypoechoic at standard EUS. At CH-EUS, of the 11 lesions, 6 appeared hypoenhancing (colon cancer, sarcoma, and breast and ovarian cancer), 4 were hyperenhancing (renal cancer and lymphoma),and 1 was isoenhancing (melanoma)., Conclusions: In our population, standard EUS features of PM were unremarkable. At CH-EUS, most of the PM appeared hypoenhancing suggesting a possible malignant origin. However, a subset of PM showed hyperenhancing pattern. In the appropriate context, particularly when cancer history is present, CH-EUS may add to the differential diagnosis and potentially spare endoscopic ultrasonography with fine-needle aspiration.

Our aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence (LE). Original research articles (randomized controlled trials, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were included. All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities, anatomical subdivisions and therapeutic applications of EUS. The North of England evidence-based guidelines were used to determine LE. A total of 1089 pertinent articles were reviewed. Published research focused primarily on solid pancreatic neoplasms, followed by disorders of the extrahepatic biliary tree, pancreatic cystic lesions, therapeutic-interventional EUS, chronic and acute pancreatitis. A uniform observation in all six categories of articles was the predominance of LE III studies followed by LE IV, II b, II a, I b and I a, in descending order. EUS remains the most accurate method for detecting small (< 3 cm) pancreatic tumors, ampullary neoplasms and small (< 4 mm) bile duct stones, and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms. Detailed EUS imaging, along with biochemical and molecular cyst fluid analysis, improve the differentiation of pancreatic cysts and help predict their malignant potential. Early diagnosis of chronic pancreatitis appears feasible and reliable. Novel imaging techniques (contrast-enhanced EUS, elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis. Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy. Despite the ongoing development of extra-corporeal imaging modalities, such as computed tomography, magnetic resonance imaging, and positron emission tomography, EUS still holds a leading role in the investigation of the pancreaticobiliary area. The major challenge of EUS evolution is its expanding therapeutic potential towards an effective and minimally invasive management of complex pancreaticobiliary disorders.

Background and Aims: A prolific trend currently designates endoscopic ultrasonography (EUS) literature. We aimed to record all EUS-studies published during the past decade and evaluate them in terms of scientific quality, creating a stratification based on levels of evidence (LE)., Methods: All articles on EUS published between January 2001 and December 2010 were retrieved using a Pubmed and Cochrane Library search. Inclusion criteria were: original research papers (randomized controlled trials-RCTs, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS. Levels of evidence (LE) were assessed using the North of England evidence-based guidelines., Results: Overall, 1,832 eligible articles were reviewed. The majority (46.1%) of reports comprised retrospective descriptive studies (LE III). Expert reviews and committee reports (LE IV) accounted for 28.9%, well-designed quasi-experimental studies (LE IIb) for 20.1%, RCTs (LE Ib) for 2.4%, prospective controlled trials (LE IIa) for 1.4%, and meta-analyses (LE Ia) for 1.1% of the total. High LE (Ia-Ib) were assigned to loco-regional staging of luminal gastrointestinal cancers; mediastinal staging of lung cancer; diagnostic work-up of solid pancreatic tumors, suspected biliary obstruction and choledocholithiasis; celiac plexus neurolysis; and pancreatic pseudocysts drainage. Intermediate to low LE (IIa-IV) were assigned to submucosal tumors, pancreatic cysts, chronic pancreatitis and novel therapeutic applications (pancreato-biliary drainage, tumor ablation)., Conclusions: Diagnostic and staging EUS has matured and has proven its clinical impact on patient management. Therapeutic or interventional EUS is still evolving and more quality research and data are needed to establish EUS as the best next intervention to perform once firm evidence is available.

The literature about endoscopic ultrasonography (EUS) is still very prolific although it was introduced in the early 1980s. We aimed to review last decade's scientific production and to compare it with our earlier data about the period from 1980 to 2000. EUS publications of the period January 2001 to January 2010 were retrieved. Reviews, prospective, and retrospective studies, randomized controlled trials, meta-analyses, surveys, guidelines, and case-series were assessed. Data were collected on the subject-matter, type of publication, number of patients included, publishing journal, most recent impact factor, year of publication, and country accredited for publication. A total of 1763 relevant papers were published in more than 250 journals. The main areas of research were pancreatic disorders, tumors of the gastrointestinal wall, the extrahepatic biliary tree, submucosal lesions, lung cancer, and mediastinal masses. It is interesting to note that the therapeutic applications of EUS accounted for a new field of investigation. The majority of articles comprised retrospective trials and reviews, followed by prospective studies and case series. However, a considerable number of randomized controlled trials and meta-analyses was retrieved, which were absent in the earlier survey. United States, Europe, and Japan still possessed a pivotal role on EUS research, but an increasing number of publications has also emerged from other countries. The available literature on EUS keeps expanding, encompassing not only its well-established diagnostic role, but also novel indications and therapeutic interventions. EUS has evolved into a valuable implement of modern clinical practice, with a critical effect on patients' management. A trend toward well-structured studies is evident.

Background & Aims: Contrast harmonic echo (CHE) has been developed for endoscopic ultrasound (EUS). This new technique detects echo signals from microbubbles in vessels with very slow flow, without artifacts. We assessed whether CHE-EUS increases the accuracy of diagnosis of pancreatic solid lesions., Methods: At a tertiary-care EUS center, we examined 90 patients who were suspected of having pancreatic solid neoplasm. Radial and linear echoendoscopes were used with dedicated software for CHE. Sonovue (Bracco International BV, Amsterdam, The Netherlands) uptake, pattern, and washout were studied; data were compared for pancreatic lesions and adjacent parenchyma. The final diagnosis was obtained based on results of surgical pathology and/or EUS-fine needle aspiration (FNA) analyses., Results: The finding of a hypoenhancing mass with an inhomogeneous pattern was a sensitive and accurate identifier of patients with adenocarcinoma (96% and 82%, respectively) (49 of 51 patients with primary pancreatic adenocarcinoma had a hypoenhancing mass that was inhomogeneous and had fast washout). This finding was more accurate in diagnosis than the finding of a hypoechoic lesion using standard EUS (P < .000). Hyperenhancement specifically excluded adenocarcinoma (98%), although sensitivity was low (39%). Of neuroendocrine tumors, 11 of 13 were non-hypo-enhancing (9 hyperenhancing, 2 isoenhancing). Interestingly, CHE-EUS allowed detection of small lesions in 7 patients who had uncertain standard EUS findings because of biliary stents (n = 5) or chronic pancreatitis (n = 2). Targeted EUS-FNA was performed on these lesions., Conclusions: Detection of a hypoenhancing and inhomogeneous mass accurately identified patients with pancreatic adenocarcinoma. CHE-EUS increased the detection of malignant lesions in difficult cases (patients with chronic pancreatitis or biliary stents) and helped guide EUS-FNA. A hyperenhancing pattern could be used to rule out adenocarcinoma., (Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Biliary stents have been found to interfere with endoscopic ultrasound (EUS) tumor (T) and nodal (N) staging in patients with periampullary cancer. Our aim was to determine whether this also occurs in patients with pancreatic head cancer., Patients and Methods: We studied a consecutive series of patients who were undergoing preoperative EUS for diagnosis and staging of suspected pancreatic cancer, some of whom had biliary stents in situ and some of whom did not. The main end point was the uni- and multivariate association of biliary stenting with T and N mis-staging by EUS. The surgical T and N stages were used as gold standards., Results: A total of 65 patients were identified (19 with biliary stents in situ and 46 without). Surgical stage T4 was found more frequently in patients with stents (53% vs. 22%, P = 0.014). The T stage by EUS was correct in 85% of the patients without biliary stents and in 47% of the patients with stents. The frequency of mis-staging by EUS was significant only among patients with a biliary stent. The distribution by EUS N stage did not differ significantly from the surgical N-stage distribution in the two groups of patients. According to the multivariate analysis, patients with stents were 6.55 times more likely to be incorrectly T staged (95% confidence interval [CI] 1.69-25.49) and 3.71 times more likely to be incorrectly N staged (95% CI 1.11-12.45) than patients without stents., Conclusions: The results add support to the recommendation that EUS staging of pancreatic head neoplasms should be performed prior to stent placement.

Endoscopic ultrasonography and endoscopic ultrasonography-guided fine needle aspiration are well-established techniques, encompassing a variety of diagnostic and therapeutic applications. Along with traditional indications that constitute everyday clinical practice in all endoscopic ultrasonography centres, new indications are emerging that resemble the continuing research carried on in this field. Some of these are innovative applications, developed by highly experienced endosonographers and with a putative role for clinical practice in the near future. Others are merely experimental applications, carried out on in animal models or in highly selected groups of patients, opening up new fascinating areas of research but not for imminent introduction in clinical practice. The purpose of this review, after summarising the present indications of endoscopic ultrasonography, is to focus on the future applications and try to establish their possible advent, either in the near or in the far future.

Endoscopic ultrasonography appeared in the clinical arena almost 20 years ago and it has now become a well integrated technique in everyday hospital practice. More than 2000 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 instrumentation consists of a special endoscope, modified by a high-frequency ultrasound transducer placed on its tip, and an ultrasound driving unit. The main indications to endoscopic ultrasonography can be explained by its ability to visualize the gut wall as a multi-layer structure corresponding to histological layers. Other important indications derive from its capability of displaying, very closely, the structures and lesions surrounding the gut wall, such as the pancreato-biliary area, masses and lymph nodes. Fine-needle aspiration has become an indispensable adjunct to the technique since 1993, when it was shown to be feasible and safe to obtain tissue diagnosis in the majority of the lesions under the reach of endoscopic ultrasonography. In recent years, some authors have dealt with the practical clinical applications of endoscopic ultrasonography, validating its use in many diagnostic and staging algorithms and showing that it is cost-effective and significantly affects patient outcome.

This paper covers the literature published between June 2003 and August 2004 on endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (FNA). During this period, more than 120 original studies were published on the topic, not to mention editorials and case reports--indirect evidence of the ever-increasing importance of EUS in everyday clinical practice. However, due to limitations of space, this review will focus only on a few articles selected for their importance and originality. The studies presented deal either with the outcome of EUS--i. e., its real importance in affecting the choices physicians are faced with in their clinical work--or definitively clarify certain technical issues that have often been a matter of debate at EUS meetings. Finally, a few papers describing new potential diagnostic or interventional applications of EUS are presented. Many other relevant papers in addition to those discussed in detail are cited in the references.

This review again uses a practical arrangement of the topics of endoscopic ultrasonography (EUS) into clinical categories rather than single diseases. The clinical categories include established indications, such as staging of gastrointestinal tract cancers, differential diagnosis of submucosal tumors, evaluation of solid and cystic pancreatic masses, detection of lymph nodes, evaluation of the biliary tree, and fine-needle aspiration (FNA). In addition to established indications, surgical and investigational techniques are presented, such as fine-needle therapeutic procedures and methods of studying portal hypertension and hepatic, abdominal, and retroperitoneal masses. This year, the new techniques and instruments presented have not included new probes or endoscopes, as these have already gained wide application in published papers and clinical practice. However, new techniques capable of facilitating the use of existing equipment are discussed, such as computer-aided EUS image analysis. Finally, some fascinating studies investigated outcomes with EUS and the cost-effectiveness of the method - stimulating both endosonographers and non-endosonographers to think about current practices and ways of improving them.

Background: Anti-Helicobacter pylori therapy has been reported to cause regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma in a high percentage of patients. However, in some patients, these lesions persist despite antibiotic treatment., Aim: To determine the various endosonographic findings that may predict the regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma post-antibiotics., Methods: Seventy-six patients with Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma were studied. Follow-up data were available on 51 patients. All patients were treated with antibiotics. Participants underwent pre- and post-anti-Helicobacter pylori therapy endoscopy with gastric biopsies, followed by endoscopic ultrasonography examination of the stomach., Results: Helicobacter pylori was eradicated in 45 of 51 (88%) patients. At the 2-year follow-up, complete regression of mucosa-associated lymphoid tissue lymphoma was seen in 28 of 51 (55%) patients: 12 of 16 (75%) patients in stage T1m N0, 11 of 19 (58%) patients in stage T1sm N0, four of eight (50%) patients in stages T1m N1 and T1sm N1, and one of four (25%) patients in stage T2 N0. None of the stage T2 N1 patients achieved clinical regression., Conclusions: Endoscopic ultrasonography evaluation of gastric mucosa-associated lymphoid tissue lymphoma plays a pivotal role in the initial staging and post-treatment follow-up evaluation of these lesions. Accurate staging is essential in the determination of the optimal treatment modality.

Background and Study Aims: Endoscopic ultrasound imaging of mediastinum, gastrointestinal tract and pancreas, and endoscopic ultrasound-guided fine-needle aspiration of suspicious lesions, have now been available for several years. Although many papers have been published on endoscopic ultrasonography, a comprehensive overview of the subject matter presented has not yet been carried out. An extensive survey of the literature on endoscopic ultrasonography since its inception in the 1980 s was conducted in this study; key points are summarized., Methods: A computer-based PubMed search system was used to retrieve all available abstracts pertaining to endoscopic ultrasound from 1980 to the present. Data were collected concerning the impact factor, the various EUS instruments and fine-needle aspiration biopsy techniques used, and the subject matter, as well as the journals publishing the abstracts., Results: A total of 1259 articles were published in 65 journals: 440 (35 %) Western European studies, 404 (32 %) American studies, and 321 (26 %) Japanese studies were retrieved. The total and average impact factor per paper was highest for American papers, followed by European papers and Japanese papers. Forty-seven percent of the papers were published in Gastrointestinal Endoscopy and Endoscopy. The most frequently discussed topics concerned the staging of various malignancies, including esophageal, gastric, pancreatic, and colorectal cancer. The average sample size per paper was in the range 25 - 50. The various types of study included retrospective inquiries (25 %), reviews (24 %), prospective studies (17 %), and case reports (15 %)., Conclusions: Over the course of the past 20 years, there has been a progressive increase in the number of publications pertaining to endoscopic ultrasonography. Large-scale prospective studies are now needed to validate earlier reports. In addition, the diagnostic and therapeutic role of endoscopic ultrasound needs to be more widely publicized among physicians in all health-care fields, so that appropriate patients may be referred.

Background: EUS is highly accurate for staging gastric lymphoma. Because stage correlates to outcome, interobserver agreement is mandatory. However, previous studies suggest that interobserver agreement might vary according to T-stage. A multicenter evaluation of observer agreement with respect to endosonographic staging of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was therefore conducted., Methods: Fifty-four patients were studied; 42 were also evaluated after eradication of Helicobacter pylori infection. EUS was performed at different institutions by 10 experienced endosonographers who collected the best photographs for each examination. Interobserver agreement was estimated with kappa statistics., Results: Overall interobserver agreement for T-stage was fair, both before and after treatment (kappa = 0.38 and kappa = 0.37, respectively). Overall interobserver agreement for N-stage was substantial before treatment, but only fair after treatment (kappa = 0.63 and kappa = 0.34, respectively). The lowest values of agreement occurred with T1sm (submucosa) and T2 stage lesions., Conclusions: Interobserver agreement for staging of gastric MALT lymphoma by EUS is suboptimal before as well as after treatment of H pylori infection. This evidence suggests that gastric EUS may be more difficult technically compared with EUS of other organs. Lack of agreement is crucial because it influences the choice of therapy and assessment of response to treatment. Good interobserver agreement would permit better communication concerning the clinical status of patients, comparison of the results of different studies, and stratification of patients within clinical trials.

Twenty years after the introduction of endoscopic ultrasonography, many papers on the topic are still being published every year in the medical literature. Along with established clinical indications, such as gastrointestinal and pancreatic cancer staging and differential diagnosis of submucosal tumors, new applications have been suggested, such as mediastinal and liver tumor sampling with fine-needle aspiration. Improved accuracy and cost-effectiveness have been demonstrated in comparison with other imaging techniques. Reports of large series of fine-needle aspiration procedures have described a high level of accuracy for EUS in the diagnosis of lymph nodes and perivisceral masses. Pancreatic and ampullary tumors still represent a major challenge, as shown by numerous articles describing differential-diagnostic criteria and cytological sampling techniques. A few papers have also been published on the topic of portal hypertension, but it seems questionable whether there is any real advantage for endoscopic ultrasonography over traditional endoscopy here. New techniques such as radiofrequency tumor ablation are promising, while others such as three-dimensional imaging and the use of contrast enhancement have not yet met with routine clinical application. Finally, some of the papers published during the last year have studied the technique of endoscopic ultrasonography itself, dealing with issues of outcome, current clinical availability and use, and the learning curve. Evidently, endoscopic ultrasonography is still widely underused - not only among general practitioners and physicians in other specialties, but even by gastroenterologists. Although endoscopic ultrasonography is already 20 years old, considerable efforts are still needed, therefore, to ensure that it becomes more widely accepted in clinical practice.