Contrast Harmonic Endoscopic Ultrasonography Research Articles

Approach to Pancreatic Head Mass in the Background of Chronic Pancreatitis.

Chronic pancreatitis (CP) is a known risk factor for pancreatic cancer. CP may present with an inflammatory mass, and differentiation from pancreatic cancer is often difficult. Clinical suspicion of malignancy dictates a need for further evaluation for underlying pancreatic cancer. Imaging modalities remain the mainstay of evaluation for a mass in background CP; however, they have their shortcomings. Endoscopic ultrasound (EUS) has become the go-to investigation. Adjunct modalities such as contrast-harmonic EUS and EUS elastography, as well as EUS-guided sampling using newer-generation needles are useful in differentiating inflammatory from malignant masses in the pancreas. Paraduodenal pancreatitis and autoimmune pancreatitis often masquerade as pancreatic cancer. In this narrative review, we discuss the various modalities used to differentiate inflammatory from malignant masses of the pancreas.

Advanced Imaging of the Biliary System and Pancreas.

Despite advances in noninvasive techniques for imaging the pancreaticobiliary system, several disease processes including indeterminate biliary strictures as well as neuroendocrine tumors, inflammatory pseudotumors, and complex cysts of the pancreas remain difficult to characterize. New endoscopic imaging technologies have emerged to address these challenges. Cholangioscopy and intraductal ultrasound (IDUS) are powerful tools to characterize subtle biliary concretions and strictures. Confocal Laser Endomicroscopy (CLE) and Optical Coherence Tomography (OCT) are emerging approaches for the most difficult biliary lesions. Contrast harmonic endoscopic ultrasound (CH-EUS), elastography, and 3D-EUS are improving the approach to subtle pancreatic lesions, particularly in the context of indeterminate tissue sampling. Pancreatoscopy, pancreatic IDUS, and intracystic CLE hold promise to further improve the assessment of pancreatic cysts. We aim to comprehensively review the emerging clinical evidence for these innovative endoscopic imaging techniques.

Contrast Harmonic Endoscopic Ultrasound in Pancreatic Diseases

Endoscopic ultrasound (EUS) was first described in 1986, with the aim of overcoming the problems affecting transabdominal ultrasound imaging, mainly problems related to the interposition of gas, and artifacts produced by bone or fat. Now, EUS can be considered as the best method for the analysis of pancreatic diseases, overtaking the diagnostic accuracy of computed tomography and magnetic resonance imaging. However, fundamental B-mode imaging is limited for the diagnosis of solid pancreatic lesions, because most of them are depicted as heterogeneous and hypo-echoic, and it is difficult to differentiate between benign and malignant lesions. Similar to how perfusion patterns obtained by computed tomography or magnetic resonance imaging after injection of contrast agents allow for the characterization of focal lesions, EUS has also recently been introduced to the use of contrast agents for performing contrast-enhanced harmonic EUS (CEH-EUS), which has the capability to distinguish the type of perfusion between lesions and surrounding tissue. CEH-EUS has shown its usefulness for the diagnosis and characterization of solid pancreatic lesions. Moreover, CEH-EUS is also highly accurate for distinguishing non-neoplastic from neoplastic cysts in pancreatic lesions. Another potential role of CEH-EUS is its ability to direct EUS-guided tissue acquisition.

New horizons in the endoscopic ultrasonography-based diagnosis of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are increasingly being identified because of the widespread use of high-resolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography (EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.

Diagnostic Endoscopic Ultrasound: Technique, Current Status and Future Directions.

Endoscopic ultrasound (EUS) is now well established as an important tool in clinical practice. From purely diagnostic imaging, it has progressed to include tissue acquisition, which provided the basis for therapeutic procedures. Even as interventional EUS developed, there has been ongoing progress in EUS diagnostic capabilities due to improved imaging systems, better needles for tissue acquisition and development of enhanced imaging functions such as contrast harmonic EUS (CHEUS) and EUS elastography. EUS is well established for differentiation of subepithelial lesions, for T-staging of luminal gastrointestinal and pancreaticobiliary malignancies, for differentiation of benign pancreaticobiliary disorders and for diagnostic tissue acquisition, which can be achieved by EUS-guided fine needle aspiration or by EUS-guided fine needle biopsy using dedicated biopsy needles. This review briefly describes the technique of performing EUS and then discusses its clinical utility in terms of gastrointestinal cancer staging, the evaluation of pancreaticobiliary disorders and tissue acquisition. Enhanced imaging techniques such as CHEUS and EUS elastography are briefly reviewed.

Subharmonic and Endoscopic Contrast Imaging of Pancreatic Masses: A Pilot Study.

To use subharmonic imaging (SHI) to depict the vascularity of pancreatic masses compared to contrast-enhanced endoscopic ultrasound (EUS) and pathologic results. Sixteen patients scheduled for biopsy of a pancreatic mass were enrolled in an Institutional Review Board-approved study. Pulse-inversion SHI (transmitting/receiving at 2.5/1.25 MHz) was performed on a LOGIQ 9 system (GE Healthcare, Milwaukee, WI) with a 4C transducer, whereas contrast harmonic EUS (transmitting/receiving at 4.7/9.4 MHz) was performed with a radial endoscope (GF-UTC180; Olympus Corporation, Tokyo, Japan) connected to a ProSound SSD α-10 scanner (Hitachi Aloka, Tokyo, Japan). Two injections of the contrast agent Definity (Lantheus Medical Imaging, North Billerica, MA) were administrated (0.3-0.4 and 0.6-0.8 mL for EUS and SHI, respectively). Contrast-to-tissue ratios (CTRs) in the mass and an adjacent vessel were calculated. Four physicians independently scored the images (benign to malignant) for diagnostic accuracy and inter-reader agreement. One patient dropped out before imaging, leaving 11 adenocarcinomas, 1 gastrointestinal stromal tumor with pancreatic infiltration, and 3 benign masses. Marked subharmonic signals were obtained in all patients, with intratumoral blood flow clearly visualized with SHI. Significantly greater CTRs were obtained in the masses with SHI than with EUS (mean ± SD, 1.71 ± 1.63 versus 0.63 ± 0.89; P = .016). There were no differences in the CTR in the surrounding vessels or when grouped by pathologic results (P > .60). The accuracies for contrast EUS and SHI were low (<53%), albeit with a greater κ value for SHI (0.34) than for EUS (0.13). Diagnostic accuracy of contrast EUS and transabdominal SHI for assessment of pancreatic masses was quite low in this pilot study. However, SHI had improved tumoral CTRs relative to contrast EUS.

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

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.

Endoscopic ultrasonography using new functions for pancreatobiliary diseases: current status and future perspectives.

A new endoscopic ultrasound processor (EU-ME2 Premier Plus) has recently been developed. It improves fundamental imaging and enables three new functions; namely, tissue harmonic echo (THE), elastography, and contrast harmonic endoscopic ultrasonography (CH-EUS). However, many aspects regarding the usefulness of these three functions in the diagnosis of pancreatobiliary diseases remain unknown. In connection with and prior to the convening of Endoscopy Forum Japan 2014, endoscopic ultrasonography using EU-ME2 Premier Plus was carried out for pancreatic, bile duct, and gallbladder cases at 12 participating institutions (Japan [n = 10]; other Asian countries [n = 2]). A questionnaire survey was conducted regarding the usefulness of EU-ME2 Premier Plus for each EUS case. In addition, participants' views were surveyed by asking them to vote as to whether or not the three functions of EU-ME2 Premier Plus were useful for several items under pancreatic, bile duct, and gallbladder indications. According to the participants' views, THE (particularly THE-P mode) is essential for the diagnosis of cystic lesions. Many participants viewed elastography as useful in only extremely limited cases. Although CH-EUS was not considered useful for all cases, its indications covered a broad range. Additional studies are warranted to clarify the functions of EU-ME2 Premier Plus in more detail.

665 Contrast Harmonic Endoscopic Ultrasonography Is Able to Predict Aggressivity in Pancreatic Neuroendocrine Tumors

665 Contrast Harmonic Endoscopic Ultrasonography Is Able to Predict Aggressivity in Pancreatic Neuroendocrine Tumors

Contrast Harmonic Endoscopic Ultrasonography in the Characterization of Pancreatic Metastases (With Video)

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.

Mo1528 Role of Contrast Harmonic Endoscopic Ultrasonography (Ch-EUS) in the Characterization of Pancreatic Metastases

Pancreatic metastases account for 2-5 % of all pancreatic malignancies and challenge differential diagnosis versus primary pancreatic neoplasia. EUS fine needle aspiration (FNA) shows the greatest accuracy in the differential diagnosis of pancreatic masses. However, EUS-FNA may suffer from suboptimal sensitivity and low but not negligible rate of complications. Recently, CH-EUS has been reported as an useful adjunct in differential diagnosis of pancreatic tumors. Our aim was to evaluate the potential role of CH-EUS in the differential diagnosis of pancreatic metastases.

Interobserver agreement in contrast harmonic endoscopic ultrasound

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. 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. 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. 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.

State-of-the-art imaging techniques in endoscopic ultrasound

Endoscopic ultrasound (EUS) has recently evolved through technological improvement of equipment, with a major clinical impact in digestive and mediastinal diseases. State-of-the-art EUS equipment now includes real-time sono-elastography, which might be useful for a better characterization of lesions and increased accuracy of differential diagnosis (for e.g. lymph nodes or focal pancreatic lesions). Contrast-enhanced EUS imaging is also available, and is already being used for the differential diagnosis of focal pancreatic masses. The recent development of low mechanical index contrast harmonic EUS imaging offers hope for improved diagnosis, staging and monitoring of anti-angiogenic treatment. Tridimensional EUS (3D-EUS) techniques can be applied to enhance the spatial understanding of EUS anatomy, especially for improved staging of tumors, obtained through a better assessment of the relationship with major surrounding vessels. Despite the progress gained through all these imaging techniques, they cannot replace cytological or histological diagnosis. However, real-time optical histological diagnosis can be achieved through the use of single-fiber confocal laser endomicroscopy techniques placed under real-time EUS-guidance through a 22G needle. Last, but not least, EUS-assisted natural orifice transluminal endoscopic surgery (NOTES) procedures offer a whole new area of imaging applications, used either for combination of NOTES peritoneoscopy and intraperitoneal EUS, but also for access of retroperitoneal organs through posterior EUS guidance.