Echo-endoscopy: new therapeutic frontiers

Endoscopic ultrasound (EUS) has been established as a valuable diagnostic modality as it offers high-resolution imaging and fine-needle biopsy, which is essential in detecting and staging malignancies. Since the introduction of EUS-guided fine needle aspiration (EUS-FNA) in 1992, numerous novel EUS-based interventions and techniques have emerged. Currently, established interventional EUS techniques include celiac plexus block and neurolysis, drainage of pancreatic pseudocysts and pelvic fluid collections, and implantation of fiducial markers and radioactive seeds into the malignant tumors. Emerging EUS-guided experimental techniques include antitumor injection, ablation of tumors, and vascular access. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used for failed ERCP procedures or inaccessible ducts. Interventional EUS is a very promising technique with many potential applications. The future holds promise for substantial progress in EUS-guided therapeutic interventions and their applications in clinical gastroenterology.     

Current role of endoscopic ultrasound in the diagnosis and management of pancreatic cancer

Endoscopic ultrasound (EUS) has emerged as an invaluable tool for the diagnosis, staging and treatment of pancreatic ductal adenocarcinoma (PDAC). EUS is currently the most sensitive imaging tool for the detection of solid pancreatic tumors. Conventional EUS has evolved, and new imaging techniques, such as contrast-enhanced harmonics and elastography, have been developed to improve diagnostic accuracy during the evaluation of focal pancreatic lesions. More recently, evaluation with artificial intelligence has shown promising results to overcome operator-related flaws during EUS imaging evaluation. Currently, an appropriate diagnosis is based on a proper histological assessment, and EUS-guided tissue acquisition is the standard procedure for pancreatic sampling. Newly developed cutting needles with core tissue procurement provide the possibility of molecular evaluation for personalized oncological treatment. Interventional EUS has modified the therapeutic approach, primarily for advanced pancreatic cancer. EUS-guided fiducial placement for local targeted radiotherapy treatment or EUS-guided radiofrequency ablation has been developed for local treatment, especially for patients with pancreatic cancer not suitable for surgical resection. Additionally, EUS-guided therapeutic procedures, such as celiac plexus neurolysis for pain control and EUS-guided biliary drainage for biliary obstruction, have dramatically improved in recent years toward a more effective and less invasive procedure to palliate complications related to PDAC. All the current benefits of EUS in the diagnosis and management of PDAC will be thoroughly discussed.     

Role of endoscopic ultrasound in the diagnosis of patients with solid pancreatic masses

Endoscopic ultrasound (EUS) is the most sensitive imaging procedure for the detection of small solid pancreatic masses and is accurate in determining vascular invasion of the portal venous system. Even compared to the new CT techniques, EUS provides excellent results in preoperative staging of solid pancreatic tumors. Compared to helical CT techniques, EUS is less accurate in detecting tumor involvement of the superior mesenteric artery. EUS staging and EUS-guided FNA can be performed in a single-step procedure, to establish the diagnosis of cancer. There is no known negative impact of tumor cell seeding due to EUS-guided fine needle aspiration (FNA). Without FNA, EUS and additional methods are not able to reliably distinguish between inflammatory and malignant masses.     

Endoscopic ultrasound in pancreatic diseases

There are many indications for the use of endoscopic ultrasound (EUS) in the management of patients with pancreatic diseases. High-resolution imaging of the pancreas is achievable due to the close proximity between luminal structures and the pancreas. Since its introduction, EUS has had a significant impact on the diagnosis of pancreatic diseases. The detection of small lesions and neuroendocrine pancreatic tumors as well as the preoperative staging of pancreatic adenocarcinoma have been improved employing EUS. For the detection of small pancreatic tumors <2 cm in diameter, EUS appears to be the most sensitive method. EUS adds significant information to the differential diagnosis between pancreatic cancer and chronic pancreatitis, and it may be further enhanced by EUS-guided fine-needle aspiration. While the role of EUS in distinguishing between benign and malignant cystic pancreatic tumors is under discussion, EUS-guided drainage of pancreatic pseudocysts is an accepted treatment option for symptomatic individuals. One of the most important advantages of EUS apart from tumor staging is the early detection of chronic pancreatitis. EUS is as good as endoscopic retrograde cholangiopancreatography in diagnosing chronic pancreatitis in advanced stages. In early stages of the disease, when the ductal system remains normal, EUS appears to be a superior diagnostic modality because it can detect features of chronic pancreatitis in the parenchyma not visible by other techniques.     

EUS-Guided Antitumor Therapy for Pancreatic Tumors

Endoscopic ultrasound (EUS) is a very useful modality for the diagnosis and staging of pancreatic masses. With the advent of EUS-guided fine-needle aspiration technology, this modality has made a tremendous leap from imaging modality to histologic diagnosis and therapeutic intervention. EUS offers high-resolution images of and unparalleled access to the pancreas. After locating the tip of the echoendoscope in the duodenum or stomach, several drugs or local treatment modalities can be delivered directly into the pancreas. EUS-guided ethanol lavage with/without paclitaxel injection has been tested for the treatment of cystic tumors of the pancreas, with complete resolution of cystic tumor being observed in up to 70-80% of patients. Ethanol injection is also performed for the management of solid neuroendocrine tumors of the pancreas. Various type of EUS-guided injection have also been investigated for the treatment of pancreatic cancer. An activated allogenic mixed lymphocyte culture (Cytoimplant) was injected in patients with advanced pancreatic cancer. A replication-deficient adenovirus vector carrying the tumor necrosis factor-alpha gene was also delivered intratumorally by EUS. ONYX-015 is an oncolytic attenuated adenovirus that exhibits replication preferentially in malignant cells, causing cell death, and this has also been injected into pancreatic cancers under EUS guidance. EUS-guided local ablation therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy are also under investigation. EUS-guided fine-needle injection for various solid or cystic lesions is a rapidly expanding field. This article reviews the various applications of EUS for the treatment of pancreatic tumors.     

The role of endoscopic ultrasonography in the diagnosis and management of pancreatic cancer

EUS with FNA is highly sensitive and specific for diagnosing pancreatic cancer. However, in certain situations, such as in patients with chronic pancreatitis, this high sensitivity and specificity can significantly diminish. The use of new technology, such as EUS elastography, CE-EUS, and gene mutations detection in FNA specimens, can help to differentiate chronic pancreatitis from pancreatic cancer. EUS has evolved from a diagnostic procedure to a therapeutic intervention in pancreatic cancer. EUS-guided fiducial insertion and EUS-guided delivery of antitumor agents, in addition to celiac plexus neurolysis, are the main therapeutic applications of EUS in pancreatic cancer.     

Endoscopic ultrasonography–guided transmural drainage of pseudocysts

Endoscopic ultrasonography (EUS) has emerged as an important diagnostic and therapeutic tool in management of gastrointestinal diseases. One of the most common uses of EUS is in the diagnosis, management, and treatment of pancreatic cysts and pseudocysts. EUS allows characterization of pancreatic cysts and safe drainage of pancreatic pseudocysts. This chapter will focus on indications, techniques, and outcomes of EUS-guided pseudocyst drainage.     

Endoscopic ultrasound-guided treatments: Are we getting evidence based - a systematic review

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.     

Endoscopic ultrasound-guided anterograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) may fail in 10-15% of cases. A growing percentage of such cases are due to the inaccessible papilla after gastric bypass surgery for the treatment of obesity. Endoscopic ultrasonography (EUS) offers an alternative route of access to the bile and pancreatic ducts. Using the curved linear array echoendoscope, access to the bile and pancreatic ducts is possible under real-time EUS guidance. The route of access is 'anterograde', in contrast to the 'retrograde' approach of ERCP. We have coined the term "EUS-guided anterograde cholangiopancreatography (EACP)" to cover the spectrum of EUS-guided techniques for accessing and draining the bile and pancreatic ducts. These techniques are reviewed in this paper. The literature has validated the feasibility of EACP but complication rates have been high; the safety profile of EACP must improve. This will require tools, designed for EUS-guided applications, that enable safer transenteric access and drainage.     

Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases

Endoscopic ultrasonography(EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors. In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration. The development of EUS-guided drainage of the biliopancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures. Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described. Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro-intestinal, bilio-pancreatic and lymph node lesions. In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations.     

Technology insight: Current status of endoscopic ultrasonography

Endoscopic ultrasound (EUS) has become the most accurate imaging modality for locoregional cancer staging of the gastrointestinal tract. Fine-needle aspiration (FNA) has added a new level of accuracy for EUS in nodal staging, with reported numbers in the 90% range for luminal and pancreaticobiliary disease. In addition, new non-gastrointestinal applications are being evaluated, such as the role of EUS-FNA for the staging of non-small-cell lung cancer and exploration of the posterior mediastinum. Furthermore, the same techniques that make safe tissue sampling possible are being explored for their use as interventional applications, such as EUS-guided celiac plexus neurolysis, fine-needle injection, EUS-guided pseudocyst drainage, and EUS-guided cholangiography and pancreatography. This review describes the current clinical status of EUS in gastrointestinal oncology, as well as future and novel indications and therapeutic strategies for this technology.     

What are the current and potential future roles for endoscopic ultrasound in the treatment of pancreatic cancer?

Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Due to the aggressive tumor biology and late manifestations of the disease, long-term survival is extremely uncommon and the current 5-year survival rate is 7%. Over the last two decades, endoscopic ultrasound(EUS) has evolved from a diagnostic modality to a minimally invasive therapeutic alternative to radiologic procedures and surgery for pancreatic diseases. EUSguided celiac plexus intervention is a useful adjunct to conventional analgesia for patients with pancreatic cancer. EUS-guided biliary drainage has emerged as a viable option in patients who have failed endoscopic retrograde cholangiopancreatography. Recently, the use of lumen-apposing metal stent to create gastrojejunal anastomosis under EUS and fluoroscopic guidance in patients with malignant gastric outlet obstruction has been reported. On the other hand, anti-tumor therapies delivered by EUS, such as the injection of anti-tumor agents, brachytherapy and ablations are still in the experimental stage without clear survival benefit. In this article, we provide updates on well-established EUS-guided interventions as well as novel techniques relevant to pancreatic cancer.     

Therapeutic role of endoscopic ultrasound in pancreaticobiliary disease: A comprehensive review

With the development of technology and accessories,the role of endoscopic ultrasound(EUS) has evolved from diagnostics to therapeutics. In order to characterise the therapeutic role of EUS,we searched Web of Knowledge database and reviewed articles associated with therapeutic EUS. There are two modalities for the therapeutic purpose: drainage and fine-needle injection. EUS-guided drainage is a promising procedure for the treatment of peripancreatic fluid collection and biliary obstruction; EUS-guided fine-needle injections such as celiac plexus neurolysis,for the purpose of pain relief for pancreatic cancer and chronic pancreatitis,has emerged as a promising procedure. The aim of the study was to perform a comprehensive and conscientious review on the techniques,complications and clinical outcomes of those EUS-based procedures.     

Recent advances in endoscopic ultrasonography-guided biliary interventions

Interventional endoscopic ultrasonography (EUS) based on EUS-guided fine-needle aspiration has rapidly spread as a minimally invasive procedure. Especially in patients with failed endoscopic retrograde cholangiopancreatography, EUS-guided biliary intervention is reported to be useful as salvage therapy. EUS-guided biliary interventions are carried out using three techniques: EUS-guided bilioenteric anastomosis, EUS-guided rendezvous procedure, and EUS-guided antegrade treatment. Although interventional EUS is not yet a standardized procedure, there have been recent advances in this field that address various biliary diseases. Here, we summarize the indications, techniques, clinical results of previous studies, and future perspectives.     

Endoscopic ultrasound-guided anastomosis: Is it ready for prime time?

Significant advancements in endoscopic ultrasound (EUS)-guided drainage procedures and EUS-guided anastomosis have recently been described. The described procedures include EUS-guided drainage of pancreatic fluid collections, biliary drainage, pancreatic duct drainage, gallbladder drainage, and gastroenterostomy. These procedures have been made possible with novel devices that can reduce the difficulties of the procedures and potentially reducing the risk of adverse events. The procedures are also becoming standardized, which is essential for dissemination of the techniques. Furthermore, results from randomized studies are becoming available showing definite benefits associated with these procedures. In this paper, we will provide a review on EUS-guided anastomotic procedures.     

Interventional EUS for the treatment of pancreatic cancer

Since the curved linear array echoendoscope (linear EUS) was developed in the 1990s, EUS has evolved from EUS imaging, to EUS-guided FNA, and now to EUS-guided fine needle injection (FNI), giving EUS even wider application. This advancement has brought “interventional EUS” into the pancreato-biliary field. Interventional EUS for pancreatic cancer includes delivery of contrast agents, drainage/anastomosis, celiac neurolysis (including ganglion neorolysis), radiofrequency ablation, photodynamic therapy, brachytherapy, and delivery of a growing number of anti-tumor agents. This review will focus on interventional EUS in the treatment of pancreatic cancer.     

内镜超声引导细针穿刺对胰腺癌的诊断价值

目的了解内镜超声(EUS)引导细针穿刺(FNA)对胰腺癌的临床价值及安全性。方法选择临床诊断或临床及影像学疑诊胰腺癌患者共21例,男13例,女8例,平均年龄(59.8±15.3)岁。EUS发现病变后,在实时超声引导下用超声穿刺针行FNA,对3例无法手术的胰腺癌患者行FNA同时,以无水乙醇阻滞腹腔神经丛治疗癌痛。结果B超共检出胰腺占位16例(16/21),未检出的5例中3例经CT检出,CT共检出胰腺占位19例;EUS检出全部21例胰腺占位,5例位于胰体尾,16例位于胰头。18例患者EUS-FNA获满意标本,17例诊断为胰腺癌,1例诊断为慢性胰腺炎,胰腺癌诊断敏感性为85.0%、特异性为100.0%、准确度为85.7%。3例行无水乙醇阻滞后疼痛减轻。术后发生轻度胰腺炎1例、发热1例。结论EUS能有效检出胰腺占位,结合FNA可提高诊断的特异性及准确性。     

Endoscopic ultrasound-guided interventions in special situations

Endoscopic ultrasound(EUS) was introduced in 1982 and has since become a popular advanced procedure for diagnosis and therapeutic intervention. Initially, EUS was most commonly used for the diagnosis of pancreatobiliary diseases and tissue acquisition. EUS was first used for guided cholangiography in 1996, followed by EUS-guided biliary drainage in 2001. Advancements in equipment and endoscopic accessories have led to an expansion of EUS-guided procedures, which now include EUS-guided drainage of intra-abdominal abscesses or collections, intravascular treatment of refractory variceal and nonvariceal bleeding, transmural pancreatic drainage, common bile duct stone clearance, enteral feeding tube placement and entero-enteric anastomosis. Patients with surgically altered upper gastrointestinal anatomies have greatly benefited from EUS also. This systematic review describes and discusses EUS procedures performed in uncommon diseases and conditions, as well as applications on more vulnerable patients such as young children and pregnant women. In these cases, routine approaches do not always apply, and thus may require the use of innovative and unconventional techniques. Increased knowledge of such special applications will help increase the success rates of these procedures and provide a foundation for additional advances and utilizations of the technique.     

Interventional endoscopic ultrasound and advanced endoscopic retrograde cholangiopancreatography access techniques

Advanced endoscopic retrograde cholangiopancreatography (ERCP) ductal access techniques require a higher level of skill compared to standard ERCP access maneuvers. These techniques are used in cases of standard ERCP access failures and include dual-wire techniques and precut papillotomy. Interventional endoscopic ultrasound (EUS) procedures requiring a higher level of technical skill as compared to more basic EUS procedures (eg, diagnostic EUS and EUS-fine needle aspiration) include EUS-guided drainage of pancreatic fluid collections, EUS-guided pancreaticobiliary ductal access and drainage, and EUS-guided vascular interventions. In this article, we review techniques and outcomes of advanced ERCP access techniques and of interventional EUS procedures. Issues related to training in these techniques, assessing competency in these procedures, and incorporating these highly complex and higher-risk procedures into endoscopic practice are also discussed.