The clinical impact of ultrasound contrast agents in EUS: a systematic review according to the levels of evidence.

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.

Interobserver agreement in contrast harmonic endoscopic ultrasound.

BACKGROUND AND AIM: Contrast harmonic endoscopic ultrasound (CH-EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the interobserver agreement (IA) in CH-EUS. METHODS: Fifteen endosonographers (eight experienced and seven non-experienced) from 11 Italian EUS centers evaluated 80 video-cases (40 solid pancreatic lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH-EUS, according to the degree of enhancement, the pattern of distribution and the washout of the contrast agent. IA within each group and between the two groups of observers was assessed with the Fleiss kappa statistic. RESULTS: Overall IA was moderate for the uptake and fair for the pattern of distribution and the washout. In solid pancreatic lesions, IA was moderate for the uptake and fair for the pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate for the assessment of uptake, slight for the pattern and fair for the washout. In submucosal tumors, IA was substantial for the uptake, slight for the pattern and fair for the washout. Non-experienced endosonographers demonstrated, in most cases, comparable IA with the experienced ones. CONCLUSIONS: Interobserver agreement among endosonographers for CH EUS was satisfactory. In particular, overall IA varied from slight to substantial, being fair in the majority of cases. Inherent structural features of the lesions, as well as technical differences between the variables assessed, could have accounted for the fluctuation of the results. Outcomes of IA were reproducible between experienced and non-experienced endosonographers.

Levels of evidence in endoscopic ultrasonography: a systematic review.

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.

Scientific publications in endoscopic ultrasonography: changing trends in the third millennium.

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.

Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses.

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.

Laparoscopic treatment of gastric GIST: report of 21 cases and literature's review.

BACKGROUND: Although the feasibility of laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been established, various aspects are debated. This paper describes the problems of minimally invasive resection of gastric GISTs and compares this experience with an extensive literature review. STUDY DESIGN: Between August 2001 and December 2006, 21 consecutive patients undergoing laparoscopic resection of gastric GISTs were enrolled in a prospective study. A literature review of laparoscopic treatment was performed on Pubmed using keywords GIST and surgery. A comparison with authors' experience with open wedge-segmental resection of GISTs (25 cases from November 1995 to December 2000) was also carried out. Statistical analysis was based on chi-squared test and t Student evaluation. RESULTS: Twenty-one patients, mean age 50.1 years (range, 34-68 years), were submitted to laparoscopic wedge- segmental gastric resections. Mean tumor size was 4.5 cm (range, 2.0-8.5 cm). Mean operative time was 151 min (range, 52-310 min), the mean blood loss was 101 mL (range, 10-250 mL), and the mean hospital stay was 4.8 days (range 3-7 days). There were no major operative complications or mortalities. All lesions had negative resection margins. At a mean follow-up of 35 months, all patients were disease-free. Morbidity, mortality, length of stay, and oncologic outcomes were comparable to the open surgery retrospective evaluation (p=not significant). CONCLUSIONS: As found also in the literature review, the laparoscopic resection is safe and effective in treating gastric GISTs. Given these findings as well as the advantages afforded by laparoscopic surgery, a minimally invasive approach should be the preferred surgical treatment in patients with small- and medium-sized gastric GISTs.

EUS liver assessment using contrast agents and elastography.

Transabdominal-US is the first-line imaging modality used to assess the whole liver parenchyma and vascularization; EUS assessment of the liver is incomplete and is not sufficient to rule out the presence of focal liver lesions. On the other hand, due the high diagnostic yield in detecting very small (< 1 cm) lesions, EUS is considered complementary to radiological imaging techniques for the investigation of liver parenchyma. Scarce data are available regarding the investigation of liver parenchyma using both EUS-elastography (EUS-E) and CH-EUS. The aim of this review is to evaluate the clinical role of image enhancement techniques, namely EUS-E and contrast harmonic-EUS (CH-EUS), for the evaluation liver diseases. Despite a potential interest for the application of EUS-E in the assessment of liver diseases, available evidence relegates this technique only to research areas, such as the differential diagnosis between benign and malignant focal liver lesions and the quantification of liver fibrosis in diffuse parenchymal diseases. With the future introduction of EUS shear-wave elastography, interesting data can be obtained for the assessment of liver fibrosis during real-time EUS evaluation. The usefulness of CH-EUS for the evaluation of liver disease is limited by the intrinsic EUS ability to explore only the left lobe and a small part of the right lobe. CH-EUS could be used to increase the diagnostic ability of EUS for the detection and characterization of small lesions and for guiding tissue sampling. Targeting EUS-guided treatments with either EUS-E or CH-EUS might represent potential future applications.

Basics in Endoscopic Ultrasound Part 2: EUS-guided Sampling and Therapeutic Applications.

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.

Basics in Endoscopic Ultrasound Part 1: Diagnostic Indications and Tissue Sampling.

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.

Catheter probe extraductal ultrasound (EDUS) exploration of the common bile duct is safe in elderly patients with suspicion of choledocholithiasis after distal gastrectomy.

PURPOSE: Post-surgical upper gastrointestinal anatomy may hamper a complete bilio-pancreatic evaluation with a standard echoendoscope. The aim of this study was to assess the role of catheter probe extraductal ultrasound (EDUS) for the evaluation of the common bile duct (CBD) in patients who are status post-gastric surgery and who are suspected of having choledocholithiasis. METHODS: We retrospectively analyzed patients with a prior history of gastric surgery, who underwent EDUS for a suspicion of CBD obstruction. For each patient, technical success, accuracy, and safety were recorded. In case of a positive finding of CBD stones, endoscopic retrograde cholangiopancreatography (ERCP) was performed. In case of other findings or a negative EDUS, computed tomography or magnetic resonance cholangiopancreatography (MRCP) was performed as appropriate. RESULTS: EDUS was technically successful in all the 11 patients with a Billroth II gastrectomy, while it failed in all the 5 patients with Roux-en-Y gastric surgery. EDUS accuracy was 100% (3 true-positive and 8 true-negative cases). CBD stones, confirmed and successfully extracted at ERCP, were found in two patients, while in one patient EDUS showed a CBD stenosis that was treated with a plastic stent during ERCP; computed tomography at follow-up was negative for cancer. EDUS was correctly negative in 8 patients, as confirmed by MRCP. CONCLUSIONS: EDUS may represent an accurate and safe alternative to standard endoscopic ultrasonography and MRCP for the detection of CBD stones in elderly patients who are status post-Billroth II gastric surgery.

Role of contrast harmonic-endoscopic ultrasound in pancreatic cystic lesions.

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.

Contrast enhancement and elastography in endoscopic ultrasound: an update of clinical applications in pancreatic diseases.

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.

Contrast Harmonic-Endoscopic Ultrasound Is Useful to Identify Neoplastic Features of Pancreatic Cysts (With Videos).

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.

Reliability of endoscopic ultrasound in predicting the number and size of common bile duct stones before endoscopic retrograde cholangiopancreatography.

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.

Pancreatic necrosectomy: an evidence-based systematic review of the levels of evidence and a comparison of endoscopic versus non-endoscopic techniques.

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.

Endoscopic ultrasonography: current clinical role.

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.