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Supplementary Figure 1. Fagan Nomogram analysis. A line is drawn connecting the pre-test probability and the point on the middle vertical line corresponding to the likelihood ratio for the test result, represented by a range of test results (boxes). This line is extended to intersect with the right-hand vertical line, which gives the post-test probability. This point is the new estimate of probability that the patient has the disease. A) Nomogram for post-test probability of having a tumor. B) Nomogram for post-test probability of having a tumor or high-risk adenoma.

Background: DNA integrity analysis could represent an alternative approach to the early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA) in stools was extracted using a manual approach and analyzed by capillary electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the detection of early malignant lesions in a population undergoing colorectal cancer screening.Methods: From 241 stool samples, DNA was extracted using manual and semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA approach with the iFOBT report.Results: Nonparametric ranking statistics were used to analyze the relationship between the median values of RT FL-DNA and the clinicohistopathologic characteristics. The median values of both variables were significantly higher in patients with cancer than in patients with noncancerous lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods provided more accurate diagnostic information and were able to identify subgroups at varying risks of cancer.Conclusions: The combination of the semiautomatic extraction system and RT FL-DNA analysis improved the quality of DNA extracted from stool samples.Impact: RT FL-DNA shows great potential for colorectal cancer diagnosis as it is a reliable and relatively easy analysis to perform on routinely processed stool samples in combination with iFOBT. Cancer Epidemiol Biomarkers Prev; 23(11); 2553–60. ©2014 AACR.

Supplementary Table 1. CRC and CRC+HRA prevalence as a function of different FL-DNA cut offs in negative-positive iFOBTs separated by the median value of all positive iFOBTs

To evaluate the potential role of contrast harmonic endoscopic ultrasound (CH-EUS) in the differential diagnosis of pancreatic cysts and detection of malignancy.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.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).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.

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.

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.

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.

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

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.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.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).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.

Background and aims Endoscopic ultrasound-guided fine needle aspiration is routinely used in the diagnostic work up of pancreatic cancer but has a low sensitivity. Studies showed that Pancreatic Duodenal Homeobox-1 (PDX-1) is expressed in pancreatic cancer, which is associated with a worse prognosis. We aimed to verify whether the assessment of PDX-1 in endoscopic ultrasound-guided fine needle aspiration samples may be helpful for the diagnosis of pancreatic cancer. Methods mRNA of 54 pancreatic cancer and 25 cystic lesions was extracted. PDX-1 expression was assessed by Real-Time PCR. Results In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative. The positivity was associated with a probability of 0.98 (95% CI 0.90–1.00) of having cancer and the negativity with one of 0.08 (95% CI 0.01–0.27). The probability of cancer rose to 1.00 (95% CI 0.97–1.00) for patients positive to both PDX-1 and cytology and fell to 0.0 (95% CI 0.00–0.15) in patients negative for both. Conclusions PDX-1mRNA is detectable in samples of pancreatic cancer. Its quantification may be helpful to improve the diagnosis of pancreatic cancer.

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 enhance- ment, the pattern of distribution and the washout of the contrast agent. IAwithin each group and between the two groups of observers was assessed with the Fleiss kappa statistic. Results: Overall IAwas 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 IAwith the expe- rienced ones. Conclusions: Interobserver agreement among endosonographers for CH EUS was satis- factory. 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.

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.

Delayed esophageal metallic stent migration after a neo-adjuvant therapy of advanced esophageal cancer is a relatively frequent event, which is sometimes due to tumor response to chemotherapy. Stent migration in the stomach is usually asymptomatic but it can cause potentially life-threatening complications as bowel obstruction or perforation. Most gastric migrations can be managed endoscopically; however endoscopic stent removal could also be a risky procedure due to hemorrhage or esophageal perforation. This case report describes a safe and quick endoscopic method to remove a migrated esophageal metallic stent from the stomach using a protection hood mounted on the tip of the endoscope.

Endoscopic ultrasound (EUS) has excellent overall sensitivity (94 %) and specificity (95 %) for the diagnosis of choledocholithiasis [1]. EUS is also very accurate in the diagnosis of common bile duct (CBD) sludge, with a sensitivity up to 90 % and specificity of 97 % (personal data). By performing EUS first in patients with suspected CBD stones, endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) may be safely avoided in two-thirds of the cases. On the other hand, ERCP with EST is appropriate when the presence of CBD stones has been documented by EUS. As a result, a EUS-based selection of patients for therapeutic ERCP significantly reduces complication rates [2, 3]. The American Society of Gastrointestinal Endoscopy...

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.

Background Gastric juice is usually discarded during upper-GI endoscopy. Objective By using a novel device, the Mt 21-42, we evaluated the potential of this important organic fluid in clinical practice, exploring its contribution to the diagnosis of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa (AGOM). Design and Patients A multicenter study (17,907 patients; 10 endoscopy units) estimated the frequency of diagnosis of AGOM and H pylori infection in routine endoscopic practice. A prospective study (216 patients) at 1 of these units aimed to determine the real prevalence of these conditions and the possible benefits of gastric juice analysis. We considered gastric juice pH and ammonium concentration, endoscopic and histologic features, serologic parameters for atrophy and H pylori , gastric acid secretion, and costs. Results We found that H pylori infection and, even more markedly, AGOM were greatly underdiagnosed in routine endoscopic practice (20.1% and 0.8% vs 49.1% and 12.5% in the prospective study, respectively), because of the intrinsic limitations of the conventional tests and lack/inappropriateness of biopsy planning. Gastric-juice analysis proved to be a cheap, simple, and effective way to prevent such underdiagnosis and allowed detection of atrophic gastritis and H pylori in 96% and 98% of cases, and saved costs (cost-effectiveness ratio 209 vs 274-5047). Conclusions Gastric juice provided a valuable source of clinicopathologic information that, properly analyzed, allowed detection of the main risk factors for gastric cancer ( H pylori and atrophic gastritis), overcoming the diagnostic limitations associated with these conditions and also producing time and cost savings.

Soon after the first report in 1992 [1], EUS-FNA became an indispensable tool to obtain tissue diagnosis in the majority of the lesions within its reach [2]. The two main benefits of endoscopic ultrasound (EUS) are its superior accuracy in the detection of lesions\2–3 cm in diameter within 4 cm from the transducer, compared with extracorporeal imaging techniques, and the possibility of tissue acquisition by EUS-guided fine needle aspiration (FNA). EUS-FNA can facilitate diagnosis when tissue is acquired from the primary tumor and is useful for staging when tissue is acquired from suspicious lymph nodes or suspected metastatic lesions. Pancreatic solid and cystic masses and gastrointestinal subepithelial tumors are typical targets of diagnostic EUS-FNA. Non-peritumoral lymph nodes, liver, and adrenal gland lesions are examples of the utility of EUS-FNA for staging. Moreover, EUS-FNA of either a lymph node or a suspected metastasis (e.g., in the liver) may enable simultaneous diagnosis and staging in a patient whose primary tumor cannot be sampled. EUS-FNA is particularly useful in the lower gastrointestinal tract where few alternatives exist, such as extracorporeal or laparoscopic sampling, for tissue acquisition from pelvic lesions, as opposed to upper gastrointestinal and mediastinal lesions, where percutaneous and surgical techniques are still in use. The main indications for pelvic EUS include rectal cancer preoperative staging and post-surgical surveillance, the differential diagnosis of subepithelial tumors, the diagnosis and sampling of perirectal solid and cystic masses, and the evaluation of fecal incontinence and perianal disease. Since male and female abnormalities of the genitourinary tract are not usually part of gastroenterologist’s armamentarium, they will not be included in the discussion. In this issue of Digestive Diseases and Sciences, Han et al. [3] draw attention to the accuracy and safety of pelvic EUS-FNA. By means of systematic literature review and meta-analysis during 2000–2014, data were obtained from 10 studies deemed of high quality according to the method of quality assessment of studies and data extraction (QUADAS). Evidently, the investigators scrupulously contacted the corresponding authors of the selected articles in order to extract the individual data for pelvic lesions or to calculate the specific operating characteristics in 7 of the 10 studies. Overall, 246 patients were included in the analysis. The pooled sensitivity and specificity of EUSFNA were 89 % (95 % confidence interval, 83–94 %) and 93 % (95 % confidence interval, 86–97 %), respectively, and the area under the summary receiver operating characteristic (SROC) curve was 0.96. Nonetheless, the authors stressed a potential publication bias indicated by the significant asymmetry of the Deek’s funnel plot, as it is often the case in the EUS literature. In other words, since studies with positive results are more likely to be published than the negative ones, the real sensitivity and specificity of EUS-FNA in practice may be lower than the figures reported in this meta-analysis. The overall adverse events rate was 1.7 % with one post-biopsy hemorrhage, which was managed conservatively, and two patients with cystic lesions who developed abscesses after EUS-FNA and required percutaneous drainage. Just after the end of the consideration period of the metaanalysis, a large American study was published specifically & Pietro Fusaroli pietro.fusaroli@unibo.it

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

Background and Objectives: Failures of endoscopic ultrasound (EUS) imaging of the head of the pancreas (HOP) and the common bile duct (CBD) have been reported in up to 50% of patients with status postsurgery (e.g., Billroth II and Roux-en-Y). This is attributable to inability to intubate the afferent limb or the duodenum. Recently, a forward-view (FV) echoendoscope has become available. The frontal endoscopic and ultrasound fi eld of view theoretically allow easier manipulation throughout the gastrointestinal tract compared to the traditional echoendoscopes. The aim of our study was to evaluate the safety and performance of the FV echoendoscope for the investigation of the biliary tree and the pancreas, including fi ne-needle aspiration (FNA), in patients with surgically altered upper gastrointestinal anatomy. Patients and Methods: This was a retrospective evaluation of a prospectively maintained database. All EUS procedures were performed at our institution by one experienced endosonographer from March to September 2009 under conscious sedation. The FV echoendoscope was used for all procedures. Results: Twenty-fi ve (25) out of 37 presented status post-Billroth II and 12 out of 37 with status post-Roux-en-Y surgery. Overall, HOP and CBD were adequately visualized in 28 out of 37 (75.7%). All the failures occurred in the Roux-en-Y patients. EUS-FNA was successfully performed in 16 patients. No adverse events were observed. Conclusions: The FV echoendoscope proved to be safe and effective in reaching the periampullary area in patients with previous Billroth II, allowing complete exploration of the HOP and the CBD and performance of EUS-FNA. However, FV EUS was unsuccessful in the majority of patients with Roux-en-Y, which still remains a challenging condition.

The clinical outcome of patients receiving liver transplantation could be significantly affected by biliary complications, including strictures, leaks, stones and bilomas; early diagnosis and treatment of these conditions lead to markedly reduction in morbidity and mortality. Therapeutic gold standard is represented by conservative approaches, both endoscopic and percutaneous, based on the type of biliary reconstruction, the local availability of the procedures and specific expertise. In patients with previous transplantation, the difficult biliary access and the possible presence of concomitant complications (mainly strictures) further restrict the efficacy of the endoscopic and percutaneous treatments; on the other hand, surgery should generally be avoided because of the even increased morbidity and mortality due to technical and clinical issues. Here we review the most common biliary complications occurring after liver transplantation and discuss available treatment options including future perspectives such as endoscopic ultrasound-guided biliary access in patients with Roux-en-Y choledocho-jejunostomy or extracorporeal shock wave lithotripsy for difficult stones.

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.

L’Echoendoscopie (EE) et la ponction aspiration a l’aiguille fine guide par EE recouvrent une grande variete d’applications diagnostiques et therapeutiques. Outre les applications bien etablies, de nouvelles indications voient le jour. Certaines sont novatrices, developpees par des endosonographistes les plus experimentes avec dans un futur proche, un role presume en pratique clinique. D’autres ne sont que des applications experimentales, menees sur des modeles animaux ou sur un groupe de patients hautement selectionnes. Celles-ci ouvrent neanmoins une voie fascinante de recherche sachant toutefois qu’elles ne seront pas rapidement introduites dans la pratique clinique. Endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (FNA) encompass a variety of diagnostic and therapeutic applications. Along with established indications, new indications are emerging. Some 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 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.

Background: Gastric juice may give important clinico-pathological information, but measurements in this medium are difficult. In this study we present and validate an innovative device (Mt 21-42) performing gastric juice analyses during endoscopy and proposed for the endoscopic diagnosis of Helicobacter pylori infection and hypo/achlorhydria. Methods: Analyses on both aqueous solutions (80 pH buffer + 120 ammonium chloride samples) and human gastric juice were carried out to assess the measuring performance of Mt 21-42 on the ideal and real matrix, respectively. Matrix spike and manipulation tests were also performed to investigate the matrix effect of gastric juice and to evaluate the consequences of its manipulation on the measurements. Furthermore, preliminary clinical tests were performed to evaluate the clinical potentiality of the device. Results:Mt 21-42 showed a good measuring performance on ideal matrix (coefficient variation: pH = 1.3%, ammonium = 2.1%) and real matrix (coefficient variation: pH = 1.2%, ammonium = 1.9%). Analyses on gastric juice excluded a substantial matrix effect (percent recovery =96.5–98.7%) but demonstrated a significant influence of manipulation procedures (p < 0.05). Conclusions: Human gastric juice does not have a substantial matrix effect for pH and ammonium determination, but its manipulation may affect the measurement of these components. Mt 21-42 represents a precise instrument for the measurement of gastric juice and a potential precious tool for the endoscopic detection of H. pylori infection and hypo/achlorhydric conditions.

The most common primary lymphoma of the gastrointestinal tract is B-cell lymphoma arising from mucosa-associated lymphoid tissue known as MALT lymphoma. Although the majority of these lesions affect the stomach and are associated with Helicobacter pylori organisms, sites other than the gastrointestinal tract may be affected. This case report describes a patient with concomitant laryngeal MALT lymphoma and Helicobacter pylori-related gastric MALT lymphoma derived from the same clone as confirmed by PCR. Treatment of Helicobacter pylori infection in this patient using antibiotics led to regression of both lesions. This patient remains in remission at 46-month follow-up. This is the first case report on the regression of a laryngeal MALT lymphoma after Helicobacter pylori eradication. We suggest that all patients presenting with extragastric MALT lymphoma should undergo upper gastrointestinal endoscopy with gastric biopsies for the determination of Helicobacter pylori status and presence of concomitant gastric MALT lymphoma, followed by a course of anti-Helicobacter pylori antibiotic therapy. Nonresponders may subsequently be considered for surgery and/or chemo/radiation therapy.

Although its incidence varies greatly between Eastern and Western countries, gastric carcinoma still represents the second leading cause of cancer deaths worldwide. Despite modern surgical techniques allow for high curative resection rates, long-term survival curves are still very disappointing. For this reason, neoadjuvant radiochemotherapy regimens are being increasingly adopted in attempt to improve the survival of patients with advanced gastric cancer. In order to identify which patients should be allocated to preoperative treatments, it is crucial to rely on accurate staging techniques. Soon after the first descriptions of the gastric wall 5-layer structure, - endoscopic ultrasound (EUS) became a natural candidate technique for the staging of gastric cancer. The first reports in this field demonstrated good results in terms of sensitivity and specificity both for T and N staging. - Since then, gastric cancer has traditionally been a major area of research in EUS, mainly in regard to differentiating tumor depth and detecting regional lymph node metastases, with more than 130 studies published in the period 1980-2010. In more recent years, the impact of EUS on patients’ management has also been evaluated in high-level of evidence publications such as meta-analyses and systematic reviews. - Until a few years ago, the impact of EUS in gastric cancer was limited by the lack of therapeutic options, surgery being the only opportunity either with curative or with palliative intent. The clinical arena of gastric cancer has changed substantially in recent years when treatments became more numerous. Besides the traditional surgical approach, endoscopic mucosal resection and submucosal dissection were adopted for the early stages of the disease (T1 N0) and neoadjuvant therapies (preoperative and perioperative) were introduced for the advanced stages (T3/T4 and N+). As a consequence, the potential role of EUS in gastric cancer has become much more attractive to identify the patients amenable to minimally invasive treatment, those who should undergo primary surgery, and those who need a neoadjuvant therapy. In this respect, the most recent guidelines of the National Comprehensive Cancer Network, an international highly reputed authority, have introduced EUS as a preferred modality of gastric cancer staging if no evidence of M1 disease is present at computed tomography-positron emission tomography. In this issue of the Journal, Kutup et al. reported a large single center retrospective study assessing the potential influence of EUS on decision making in gastric cancer without distant metastases. The authors’ assumption was that chemotherapy would be applied only in locally advanced cancers (T3/4 or any N+), whereas primary surgery would be performed with T1/2 N0 tumors. They analyzed the endosonographic and histopathological staging of 123 patients treated by primary surgery between 1993 and 2008. During the long study period, EUS was performed by 6 different expert endosonographers, using a radial echoendoscope at 7.5, 10 and 12 MHz. Overall T staging was correct in 45% of the patients and overall N staging was correct in 72%. Regarding the ability to differentiate between early and advanced stages of gastric cancer by EUS, distinction between T1/2 and T3/4 tumors was made with 50% sensitivity (correct recognition of T1/2) and 81% specificity (correct recognition of T3/4). According to N staging (uN0 vs. uN+), 41% of the tumors were understaged (being wrongly assigned to primary surgery), while 22% were overstaged (being wrongly assigned to neoadjuvant treatment). Overall, correct decisions between primary surgery and neoadjuvant treatment based on EUS results were made in only 55/123 patients. In the event that the treatment strategy had depended solely on EUS results, 27% of the patients would have been wrongly treated by primary surgery, because histopathology showed more advanced tumor stages, and 49% of the pat...

SUMMARY 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 postantibiotics. Methods: Seventy-six patients with Helicobacter pyloripositive 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 posttreatment 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 & Aims: Eradication of Helicobacter pylori leads to cure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in 75% of localized cases. However, prolonged follow-up is necessary to determine whether a lymphoma responds to therapy. In a small series of cases, we showed that t(11;18)(q21;q21)-positive MALT lymphomas failed to respond to H. pylori eradication. The present study aimed to verify this finding in a large cohort and confirm whether the translocation predicts the response of stage I E tumors, for which clinical staging has little prognostic value. Methods: A total of 111 patients with H. pylori –positive gastric MALT lymphoma treated with antibiotics were studied. Clinical staging was undertaken before therapy. The response of lymphoma to H. pylori eradication was determined by histologic examination of gastric biopsy specimens. Diagnostic biopsy specimens were analyzed for t(11;18)(q21;q21) by reverse-transcription polymerase chain reaction of the API2-MALT1 transcript. Results: Forty-seven of the 48 patients who showed complete regression had lymphoma at stage I E , whereas 43 of the 63 nonresponsive cases were at stage I E and the remaining cases at stage II E or above. t(11;18)(q21;q21) was detected in 2 of 48 complete-regression cases, and these positive cases showed relapse of lymphoma in the absence of H. pylori reinfection. In contrast, the translocation was present in 42 of the 63 nonresponsive cases, including 26 of 43 (60%) at stage I E . Conclusions: t(11;18)(q21;q21)-positive gastric MALT lymphomas, including those at stage I E , do not respond to H. pylori eradication. Detection of the translocation should help the clinical management of patients with gastric MALT lymphoma. GASTROENTEROLOGY 2002;122:1286-1294

Background: DNA integrity analysis could represent an alternative approach to the early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA) in stools was extracted using a manual approach and analyzed by capillary electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the detection of early malignant lesions in a population undergoing colorectal cancer screening. Methods: From 241 stool samples, DNA was extracted using manual and semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA approach with the iFOBT report. Results: Nonparametric ranking statistics were used to analyze the relationship between the median values of RT FL-DNA and the clinicohistopathologic characteristics. The median values of both variables were significantly higher in patients with cancer than in patients with noncancerous lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods provided more accurate diagnostic information and were able to identify subgroups at varying risks of cancer. Conclusions: The combination of the semiautomatic extraction system and RT FL-DNA analysis improved the quality of DNA extracted from stool samples. Impact: RT FL-DNA shows great potential for colorectal cancer diagnosis as it is a reliable and relatively easy analysis to perform on routinely processed stool samples in combination with iFOBT. Cancer Epidemiol Biomarkers Prev; 23(11); 2553–60. ©2014 AACR.

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.

In the present study we evaluated the relation among histology, H. pylori, IgG to H. pylori, gastric emptying, and acid secretion in 43 patients with fundic atrophic gastritis. On the basis of gastric acid secretion, patients were divided into three subgroups: patients with preserved acid secretion (Group 1), patients with hypochlorhydria (Group 2), and patients with achlorhydria (Group 3). Fundic glandular atrophy was more severe in hypoachlorhydric patients than in those with preserved acid secretion (P < 0.05 vs Group 2, P < 0.005 vs Group 3). H. pylori colonization was found in 94% of patients in Group 1, in 61% of patients in Group 2, and in only 8% of patients in Group 3 (P < 0.001 vs Group 1, P < 0.05 vs Group 2). Conversely, serological positivity to H. pylori was high in all three subgroups of patients (100% in Group 1, 77% in Group 2, 92% in Group 3). Gastric emptying was delayed in atrophic patients, particularly in those with hypoachlorhydria. Our data suggest that fundic atrophic gastritis represents a possible end stage of H. pylori infection, characterized by a progressive disappearance of the bacterium and a progressive deterioration of gastric functions.

Gastric carcinoid tumors are rare tumors that originate from gastric enterochromaffin-like cells in the oxyntic mucosa.1 There are three types of gastric carcinoid tumors: type I is associated with chronic atrophic gastritis, type II develops in patients with combined multiple endocrine neoplasia type 1 and the Zollinger–Ellison syndrome, and type III is sporadic.1 Although the pathogenesis of these tumors is not completely understood, hypergastrinemia has an important role in the development of types I and II.2 The multiple endocrine neoplasia type 1 gene locus may be involved in type II gastric carcinoid tumors.3,4 All three types are usually removed . . .

In the evaluation of patients suffering from portal hypertension, a knowledge of morphofunctional characteristics of the portal tree and of the shunts with the systemic circulation is fundamental. To the methods traditionally used for this purpose such as endoscopy, transabdominal sonography, angiography, magnetic resonance, and computed tomography, endosonography has been recently added as a minimally invasive and sensitive technique. By endosonography, it is possible to visualize portal branches, esophageal-gastric and rectal varices, collateral extraparietal veins, and small ascitic effusions that other diagnostic methods may miss.

To establish a correct preoperative differential diagnosis between gastric lymphoma and cancer is essential but can be difficult as endoscopic biopsies can sometimes provide a low diagnostic yield. By EUS, infiltrative carcinoma tends to show a vertical growth in the gastric wall, while lymphoma tends to show mainly a horizontal extension. EUS provides an accurate staging of gastric lymphoma, showing the exact level of infiltration and the presence of perigastric lymph nodes, thus the physician can obtain an accurate prognosis for each patient and select the best form of treatment accordingly. The response to chemoradiotherapy can also be investigated very accurately by EUS. Large gastric folds are seen in a great number of benign and malignant conditions. Diagnosis represents a clinical challenge because etiology may be extremely varied and standard biopsies are often inconclusive. Different diseases show different levels of infiltration of the gastric wall, thus a characteristic echo-pattern helps for the differential diagnosis. Endosonography, used always in combination with biopsy, allows to rule out malignancies and to select the most appropriate treatment for each patient (medical or surgical).

We describe the case of a young female referred to our unit because of acute upper abdominal symptoms. Upper gastrointestinal endoscopy showed a gastric picture resembling lymphoma or acute non-steroidal anti-inflammatory drug gastropathy (deep, large and irregular ulcers), but the clinical history and the histological examination of gastric biopsies were consistent only with acute gastritis Helicobacter pylori-correlated. The patient was treated with omeprazole and antibiotics with complete recovery. As the patient's cat had suffered from an acute gastrointestinal distress two weeks earlier, a case of zoonosis was hypothesized and an upper gastrointestinal endoscopy was performed also on the cat. Unfortunately, we were not able to detect Helicobacter pylori in the cat gastric mucosa, but only urease-producing spiral microorganisms. Possible sources of infection and pathogenetic mechanisms of the severe gastritis are discussed.

We read, with great interest, Dr Gola et al 's1 manuscript entitled “Economic analysis of costs for patients with end stage liver disease over the last year of life”, in which the authors clearly demonstrated the increased economic burden of end stage liver disease (ESLD) on health systems. This original article should not be considered only a mere analysis of costs related to ESLD but also as a starting point for future directions in this field. Liver cirrhosis is the common result of different injuries to liver tissue, leading to necroinflammation and neofibrogenesis. The prognosis of patients with chronic liver disease varies widely, depending on the presence of portal hypertension, the clinical stage, the removal of the underlying pathogenetic noxa (ie, alcohol, hepatitis C virus) or the occurrence of decompensation and other clinical events (ie, infections, kidney injury). Quality of life results reduced in almost all patients with cirrhosis because of an impairment in all the three areas of health-related QoL (HRQOL), namely, physical, psychological and social; despite these evidences, the assessment of HRQOL is frequently a marginal issue in the clinical evaluation of the patient with cirrhosis. The stage of the disease, age (older), gender (female) and cultural and socioeconomic issues significantly influence patients’ QoL. …

Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and therapeutic procedures have been performed by a curved linear array (CLA) echoendoscope since the early 1990's. This particular echoendoscope, allowing real time visualization of aspira­tion needles and of other devices, has substantially remained unchanged since its introduction to the market. In a context of rapidly expanding indications for EUS-guided procedures, a dedicated forward view (FV) echoendoscope has been developed and tested under different clinical conditions. The FV echoendoscope is equipped with front endoscopic and EUS view, allowing deployment of needles and other devices through the working channel in straight direction. Several new diagnostic and therapeutic applica­tions may thereby potentially be feasible with the FV echoendoscope and the established ones may prove easier to accomplish. The published literature with the FV echoendoscope has been systematically reviewed and the results are presented analytically and discussed in detail. EUS-FNA and therapeutic procedures, including pancreatic pseudocyst drainage, treatment of gastric fundal varices, celiac plexus neurolysis, and duct drainage were reported. The FV echoendoscope showed some unique advantages, open­ing new possibilities such as EUS-FNA in difficult gastrointestinal tracts and combined endoscopic/EUS treatment with frontal approach. However, no statistically significant evidence of superiority of the FV echoendoscope vs. the CLA echoendoscope was found in pancreatic pseudocyst drainage. No complications specifically attributable to the use of the FV echoendoscope were reported.

Le lymphome gastrique primaire represente 2 a 8 % de la totalite des lesions malignes de l’estomac et son incidence semble s’accroitre. Le lymphome gastrique a un meilleur pronostic que le carcinome de l’estomac compte tenu de sa sensibilite a la radiotherapie (RT) ou de la chimiotherapie (CT), d’ou l’importance de poser un diagnostic preoperatoire correct entre lymphome gastrique et cancer meme si generalement un tel diagnostic est considere comme difficile.

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.

It is evident that endoscopic ultrasonography could have a great clinical role in the selection of the best treatment for the individual patient because it allows the simultaneous visualization of a large part of the portal venous system and its collaterals. It has not been shown that the same kind of treatment is suitable for every patient with portal hypertension, and failure of a particular treatment may be attributable to an incorrect selection of patients. Further perspective studies with EUS in patients with portal hypertension are thus necessary in order to clearly state the cost-benefit of this technique in the management of these subjects.

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, IIb, IIa, Ib and Ia, 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.