• Diagnosis
• Endoscopic procedures
• Endoscopy
• Endosonography
• Pancreatic neoplasms
• Therapeutics

Gastric cancer (GC) represents the fourth leading cause of cancer death worldwide and many factors can influence its development (diet, geographic area, genetic, Helicobacter pylori or Epstein-Barr virus infections). High quality endoscopy represents the modality of choice for GC diagnosis. The correct morphologic classification during a high-resolution endoscopy is fundamental for oncologic diagnosis, staging and therapeutic decisions. Since its initial introduction in clinical practice the endoscopic ultrasound (EUS) has been considered a valuable tool for tumor (T-) and lymph nodes (N-) staging also in GC, in order to establish the best therapeutic strategy for the patient (e.g., upfront surgery vs neoadjuvant treatments). EUS tools as elastography, Doppler and contrast administration can improve diagnosis mainly in case of malignant lymph node evaluation. EUS has a marginal role in disease staging but has a fundamental role in case of a pre-endoscopic resection management and in the new era of endoscopic mucosal resection or submucosal dissection as minimally invasive surgery. Diagnosis and locoregional staging of GC with EUS are a method of inarguable value for the assessment of gastric wall involvement and presence of infiltrated paragastric lymph nodes. EUS can also have a role in disease restaging in those patients who have undergone neoadjuvant treatment. EUS can also have a role in the advanced phases of the disease, in facilitating palliative, minimally-invasive treatments, such as gastroenterostomy or biliary drainages. This review intends to discuss the modern role of EUS in GC topic.

• Gastric cancer
• Endoscopic ultrasound
• Endoscopic resection
• Neoadjuvant chemotherapy
• Therapeutic endoscopic ultrasound

Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer.

VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1×10¹¹ viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography.

VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption.

VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma.

EudraCT number: 2012-005556-42 and NCT02045589.

• gastrointestinal neoplasms
• immunity
• investigational
• oncolytic viruses
• therapies
• tumor microenvironment

The differential diagnosis between benign and malignant lymph nodes (LNs) has a fundamental role in the characterization and staging of malignant conditions, as well as in subsequent patients’ management. All imaging modalities (i.e. computed tomography and magnetic resonance imaging) rely mainly on size; endoscopic ultrasound (EUS) criteria based on B-mode evaluation and Doppler features fail to adequately characterize with high specificity LNs nature. The introduction of EUS-elastography and contrast-enhanced harmonic EUS are useful techniques to increase the diagnostic yield in identifying metastatic LNs, to identify which suspicious LN should require pathological characterization and, finally, to target tissue acquisition. EUS-guided tissue acquisition (EUS-TA) is increasingly being used for diagnosing lymphadenopathy whenever the characterization modifies patients’ subsequent management and when no superficial LN is accessible. Since target therapy are currently available (i.e. lung cancer, breast cancer), EUS-TA of malignant LNs could be required to identify tumor biology. In this field, both fine needle aspiration and biopsy needles are able to guarantee accurate results with almost perfect specificity and sub-optimal sensitivity. We finally propose a diagnostic algorithm based on most recent, high-level evidence for the diagnostic approach to suspected LNs assessment.

• Endoscopic ultrasound-guided tissue acquisition
• Endoscopic ultrasound-fine needle aspiration
• Endoscopic ultrasound-fine needle biopsy
• Biopsy
• Aspiration
• Cancer

• endoscopic ultrasound
• rectal cancer
• tumor staging

• biomechanics
• elastography
• endoscopic ultrasound
• extracellular matrix (ECM)
• magnetic resonance elastography
• neoadjuvant therapy
• pancreatic cancer
• pancreatic ductal adenocarcinoma (PDAC)
• tissue mechanics
• tumour microenvironment

Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.

• endoscopic ultrasonography (EUS)
• endoscopic ultrasound guided tattooing
• endoscopic ultrasound-guided fiducial placement
• endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)
• ethanol ablation
• pancreatic neuroendocrine neoplasms (PanNENs)
• radiofrequency ablation (RFA)

• strain histogram
• strain ratio
• solid pancreatic lesions

• Adult
• Aged
• Aged, 80 and over
• Elasticity Imaging Techniques/methods
• Endosonography/methods
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/diagnostic imaging
• Predictive Value of Tests
• Prospective Studies
• Rural Population
• Sensitivity and Specificity
• Urban Population
• Pancreatic Neoplasms

• endoscopic ultrasonography
• pancreatic fluid collection
• pancreatitis
• pediatric
• pediatric gastroenterologists

• Chronic pancreatitis
• diagnosis
• imaging

Endoscopic ultrasound (EUS) has a limited ability to determine the nature of solid pancreatic lesions (SPLs). Most recent ultrasound processors are provided with elastography software, which allows quantification of the tissue hardness. The aim of this study is to evaluate the effectiveness of the elasticity score (ES) and strain ratio (SR) in the differentiation of benign pancreatic lesions from malignant pancreatic lesions.

The study had a retrospective design; it included 97 patients with SPLs and 19 patients with inflammatory lesions. The ES and SR were determined during the examination; finally, EUS-guided fine needle aspiration was performed.

In this 2-year study, 116 patients were enrolled (97 with malignant lesions and 19 with benign lesions). There were 69 men and 47 women. Their median age was 55.9 years. A cut-off point was detected at SR of 7.75 with a specificity of 99.9%, sensitivity of 90.7%, positive predictive value (PPV) of 99.9%, negative predictive value (NPV) of 67.9%, and accuracy of 92.2%. After adding the ES to the SR, the cut-off point at 7.75 resulted in a specificity of 94.6%, sensitivity of 99%, PPV of 98%, NPV of 98.5%, and accuracy of 97%.

The use of the ES combined with the SR increases the accuracy of differentiation between benign and malignant SPLs and is an effective method for the evaluation of pancreatic masses.

• Elasticity imaging techniques
• Endoscopic ultrasound
• Pancreas
• Strain ratio

To evaluate the accuracy of the elastography score combined to the strain ratio in the diagnosis of solid pancreatic lesions (SPL).

A total of 172 patients with SPL identified by endoscopic ultrasound were enrolled in the study to evaluate the efficacy of elastography and strain ratio in differentiating malignant from benign lesions. The semi quantitative score of elastography was represented by the strain ratio method. Two areas were selected, area (A) representing the region of interest and area (B) representing the normal area. Area (B) was then divided by area (A). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated by comparing diagnoses made by elastography, strain ratio and final diagnoses.

SPL were shown to be benign in 49 patients and malignant in 123 patients. Elastography alone had a sensitivity of 99%, a specificity of 63%, and an accuracy of 88%, a PPV of 87% and an NPV of 96%. The best cut-off level of strain ratio to obtain the maximal area under the curve was 7.8 with a sensitivity of 92%, specificity of 77%, PPV of 91%, NPV of 80% and an accuracy of 88%. Another estimated cut off strain ratio level of 3.8 had a higher sensitivity of 99% and NPV of 96%, but with less specificity, PPV and accuracy 53%, 84% and 86%, respectively. Adding both elastography to strain ratio resulted in a sensitivity of 98%, specificity of 77%, PPV of 91%, NPV of 95% and accuracy of 92% for the diagnosis of SPL.

Combining elastography to strain ratio increases the accuracy of the differentiation of benign from malignant SPL.

• Endoscopic Ultrasound
• Elastography
• Strain Ratio
• Real Time
• Pancreatic lesions

• Diagnosis, Differential
• Elasticity Imaging Techniques/methods
• Endoscopic Ultrasound-Guided Fine Needle Aspiration
• Endosonography/methods
• Female
• Humans
• Male
• Middle Aged
• Pancreas/diagnostic imaging
• Pancreas/pathology
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/pathology
• Pancreatitis/diagnostic imaging
• Pancreatitis/pathology
• Predictive Value of Tests
• Prospective Studies
• ROC Curve
• Sensitivity and Specificity

To evaluate factors that influence the diagnostic accuracy of endoscopic ultrasound (EUS)-guided tissue acquisition for lymph node enlargement in the absence of an on-site pathologist.

A retrospective analysis of patients who underwent EUS-guided tissue acquisition for the pathological diagnosis of lymph node enlargement between April 2012 and June 2015 is reported. Tissue acquisition was performed with both cytology and biopsy needles of different calibers. The variables evaluated were lymph node location and size, number of passes and type of needle used. Final diagnosis was based on surgical histopathology or, in non-operated cases, on EUS-guided tissue acquisition and imaging assessment with a minimum clinical follow-up of 6 mo.

During the study period, 168 lymph nodes with a median size of 20.3 mm (range 12.5-27) were sampled from 152 patients. Ninety lymph nodes (53.6%) were located at mediastinum, and 105 (62.5%) were acquired with biopsy needles. The final diagnosis was benign/reactive origin in 87 cases (51.8%), malignant in 65 cases (38.7%), and lymphoma in 16 cases (9.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the detection of malignancy were 74.1%, 100%, 100% and 80.6%, respectively. The overall accuracy was 87.5% (95%CI: 81.7-91.7). No variables were independently associated with a correct final diagnosis according to the multivariate analysis.

EUS-guided tissue acquisition is a highly accurate technique for assessing lymph node enlargement. None of the variables evaluated were associated with diagnostic accuracy.

• Lymph node
• Endoscopic ultrasound
• Fine-needle aspiration
• Fine-needle biopsy
• Accuracy

• Aged
• Endoscopic Ultrasound-Guided Fine Needle Aspiration
• Feasibility Studies
• Female
• Humans
• Lymph Nodes/diagnostic imaging
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Lymphoma/diagnostic imaging
• Lymphoma/pathology
• Lymphoma/surgery
• Male
• Mediastinum
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Retrospective Studies
• Sensitivity and Specificity

Endoscopic ultrasound (EUS) has become as one the best diagnostic and therapeutic methods for the management of several intraintestinal and extraintestinal diseases, among them to highlight pancreaticobiliary indications, mediastinal evaluation, and the analysis of gastrointestinal lesions. Over the years, there has been an enormous evolution in the systems available to perform EUS. Newer processors and echoendoscopes are available nowadays, with the ability to perform new imaging analysis, such as elastography and contrast enhancement. In the present article, we will review which systems are available nowadays, focusing also in the technical advances associated.

• Solid pancreatic lesion
• endoscopic ultrasound
• stiffness
• tissue acquisition
• vascularization

The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn’s disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations.

• Endoscopic ultrasound
• Contrast-enhanced endoscopic ultrasound
• Elastography
• Colorectal cancer
• Inflammatory bowel disease
• Colorectal submucosal tumours
• Endoscopic ultrasound-guided therapy

• Adenocarcinoma/diagnostic imaging
• Adenoma/diagnostic imaging
• Colorectal Neoplasms/diagnostic imaging
• Colorectal Neoplasms/therapy
• Crohn Disease/diagnostic imaging
• Diagnosis, Differential
• Endosonography
• Humans
• Inflammatory Bowel Diseases/diagnostic imaging
• Inflammatory Bowel Diseases/therapy
• Intestines/diagnostic imaging
• Neoplasm Staging
• Predictive Value of Tests
• Reproducibility of Results

Elastography is a new ultrasound modality that provides images and measurements related to tissue stiffness. Endoscopic ultrasound (EUS) has played an important role in the diagnosis and management of numerous abdominal and mediastinal diseases. Elastography by means of EUS examination can assess the elasticity of tumors in the proximity of the digestive tract that are hard to reach with conventional transcutaneous ultrasound probes, such as pancreatic masses and mediastinal or abdominal lymph nodes, thus improving the diagnostic yield of the procedure. Results from previous studies have promised benefits for EUS elastography in the differential diagnosis of lymph nodes, as well as for assessing masses with pancreatic or gastrointestinal (GI) tract locations. It is important to mention that EUS elastography is not considered a modality that can replace biopsy. However, it may be a useful adjunct, improving the accuracy of EUS-fine needle aspiration biopsy (EUS-FNAB) by selecting the most suspicious area to be targeted. Even more, it may be useful for guiding further clinical management when EUS-FNAB is negative or inconclusive. In the present paper we will discuss the current knowledge of EUS elastography, including the technical aspects, along with its applications in the differential diagnosis between benign and malignant solid pancreatic masses and lymph nodes, as well as its aid in the differentiation between normal pancreatic tissues and chronic pancreatitis. Moreover, the emergent indication and future perspectives are summarized, such as the benefit of EUS elastography in EUS-guided fine needle aspiration biopsy, and its uses for characterization of lesions in liver, biliary tract, adrenal glands and GI tract.

• Elastography
• Endoscopic ultrasound
• Characterization
• Pancreas
• Lymph nodes

• Diagnosis, Differential
• Elasticity
• Elasticity Imaging Techniques/methods
• Endoscopic Ultrasound-Guided Fine Needle Aspiration
• Endosonography
• Humans
• Lymph Nodes/diagnostic imaging
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/pathology
• Pancreatitis, Chronic/diagnostic imaging
• Pancreatitis, Chronic/pathology
• Predictive Value of Tests
• Reproducibility of Results

• Guidelines
• endobronchial ultrasound combined with transbronchial needle aspiration (EBUS-TBNA)
• endoscopic ultrasound fine needle aspiration (EUS-FNA)
• lung cancer
• recommendations
• sarcoidosis
• staging
• training

Endoscopic ultrasound (EUS) is one of the most important modalities for the diagnosis of digestive tract diseases. EUS has been evolving ever since it was introduced. New techniques such as elastography and contrast enhancement have emerged, increasing the accuracy, sensitivity and specificity of EUS for the diagnosis of digestive tract diseases including pancreatic masses and lymphadenopathy. EUS-elastography evaluates tissue elasticity and therefore, can be used to differentiate various lesions. Contrast-enhanced EUS can distinguish benign from malignant pancreatic lesions and lymphadenopathy using the intravenous injection of contrast agents. This review discusses the principles and types of these new techniques, as well as their clinical applications and limitations.

• Endoscopic ultrasound
• Elastography
• Contrast-enhanced
• New techniques
• Digestive tract diseases

• Contrast Media
• Diagnosis, Differential
• Digestive System Diseases/diagnostic imaging
• Digestive System Diseases/pathology
• Elasticity Imaging Techniques
• Endoscopy, Digestive System/methods
• Endosonography/methods
• Humans
• Microscopy, Confocal
• Predictive Value of Tests
• Prognosis

• Gastrointestinal tract
• endoscopic
• oncology
• treatment
• ultrasonography

• BRCA1
• BRCA2
• Breast neoplasms
• Chinese
• Ethnic groups
• Genetic variation