EUS-guided Therapies Research Articles

EUS-guided therapies for primary and secondary prophylaxis in gastric varices-An updated systematic review and meta-analysis.

Gastric varices (GVs) are associated with a higher risk of uncontrolled bleeding and death when compared with esophageal varices. While endoscopic glue injection therapy has been traditionally used for secondary prophylaxis in GV, data regarding primary prophylaxis continue to emerge. Recently, EUS-guided therapies have been used in GV bleeding. We conducted a comprehensive search of several major databases from inception to June 2022. Our primary goals were to estimate the pooled rates of treatment efficacy, GV obliteration, GV recurrence, and rebleeding with EUS-guided therapy in primary and secondary prophylaxis. Overall adverse events and technical failures were assessed. Random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I2 % statistics. Eighteen studies with 604 patients were included. In primary prophylaxis, pooled rate of GV obliteration was 90.2% (confidence interval [CI], 81.1-95.2; I2 = 0). With combination EUS-glue and coil therapy, the rate was 95.4% (CI, 86.7%-98.5%; I2 = 0). Pooled rate of posttherapy GV bleeding was 4.9% (CI, 1.8%-12.4%; I2 = 0). In secondary prophylaxis, pooled rate of treatment efficacy was 91.9% (CI, 86.8%-95.2%; I2 = 12). With EUS-glue, EUS-coil, and combination EUS-glue and coil, the rates were 94.3% (CI, 88.9%-97.1%; I2 = 0), 95.5% (CI, 80.3%-99.1%; I2 = 0), and 88.7% (CI, 76%-95.1%; I2 = 14), respectively. Pooled rate of GV obliteration was 83.6% (CI, 71.5%-91.2%; I2 = 74). With EUS-glue, EUS-coil, and combination EUS-glue and coil, the rates were 84.6% (CI, 75.9%-90.6%; I2 = 31), 92.3% (CI, 81.1%-97.1%; I2 = 0), and 84.5% (CI, 50.8%-96.7%; I2 = 75), respectively. Pooled rates of GV rebleeding and recurrence were 18.1% (CI, 13.1%-24.3%; I2 = 16) and 20.6% (CI, 9.3%-39.5%; I2 = 66), respectively. Our analysis shows that EUS-guided therapy for GVs is technically feasible and clinically successful in both primary and secondary prophylaxis of GV.

Comparison of efficacy and safety of endoscopic and radiological interventions for gastric varices: A systematic review and network meta-analysis.

There is a paradigm shift in the management of gastric varices with the availability of endoscopic ultrasound and radiologic interventions. The optimal choice of intervention remains a dilemma for most treating physicians. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and ScienceDirect for studies comparing endoscopic glue injection, endoscopic thrombin injection (THB), variceal band ligation, EUS-guided coiling, EUS-guided glue injection, EUS-guided coiling with glue (EUS-C+G), balloon occluded retrograde transvenous obliteration (BRTO), and transjugular intrahepatic portosystemic shunt (TIPS) for gastric varices in adults. The data on four outcomes - obliteration of varices, rebleeding, adverse effects, and mortality - were pooled using a random-effects model. Treatment estimates were calculated as odds ratios (ORs) along with their 95% confidence interval (CI). The relative ranking of interventions for various outcomes was calculated as their surface under the cumulative ranking curve (SUCRA). We identified 34 studies (10 randomized controlled trials, 24 non-randomized trials) with 2783 patients. Based on SUCRA plots, BRTO (SUCRA 95.1) had the highest rate of variceal obliteration followed by EUS-C+G (SUCRA 80.9). The risk of rebleeding was lowest with BRTO (SUCRA 85.1) followed by EUS-C+G (SUCRA 78.8). Moderate-severe adverse effects were least likely with THB (SUCRA 92.5) and highest with TIPS (SUCRA 3.7). In terms of mortality, EUS-C+G (73.5) had the lowest probability of overall mortality followed by TIPS (69.1). In this network meta-analysis, we found BRTO and EUS-guided therapies to be superior to endoscopic glue injection. However, the level of evidence remains low.

Endo-hepatology: An emerging field.

Gastroenterologists have long been spearheading the care of patients with various forms of liver disease. The diagnosis and management of liver disease has traditionally been a combination of clinical, laboratory, and imaging findings coupled with percutaneous and intravascular procedures with endoscopy largely limited to screening for and therapy of esophageal and gastric varices. As the applications of diagnostic and therapeutic endoscopic ultrasound (EUS) have evolved, it has found a particular niche within hepatology now coined endo-hepatology. Here we discuss several EUS-guided procedures such as liver biopsy, shear wave elastography, direct portal pressure measurement, paracentesis, as well as EUS-guided therapies for variceal hemorrhage.

Endoscopic Ultrasound-Guided Treatments for Non-Variceal Upper GI Bleeding: A Review of the Literature.

Endoscopic injection of glues, clotting factors, or sclerosing agents is a well-known therapy for the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB), but less is known about endoscopic ultrasound (EUS)-guided treatments. In this setting, literature data are scarce, and no randomized controlled trials are available. We performed a review of the existing literature in order to evaluate the role of EUS-guided therapies in the management of NVUGIB. The most common treated lesions were Dieulafoy’s lesions, pancreatic pseudoaneurysms, and gastrointestinal stromal tumors (GISTs). Mostly, the treatments were performed as a salvage option after failure of conventional endoscopic hemostatic attempts, showing good efficacy and a good safety profile, also documented by Doppler monitoring of treated lesions. EUS-guided therapies may be an effective option in the treatment of refractory NVUGIB, thus avoiding radiological or surgical management. Nevertheless, available literature still lacks robust data.

Endoscopic Ultrasound-guided Gastroenterostomy: A Promising Alternative to Surgery.

Recently, with the advancement of techniques, endoscopic ultrasound-guided therapies have shown distinct advantages, especially in relieving benign and malignant gastric outlet obstruction (GOO), as well as in postoperative pancreaticobiliary diseases. Herein, we present five currently used approaches in endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumenapposing biflanged metal stents (LAMS), along with several examples of LAMS-based EUS treatment of pancreaticobiliary diseases. Compared with traditional treatment methods, EUS-guided procedures have – to some degree – shown higher success rates, both technical and clinical. Moreover, EUS-guided therapies reduce the risk of multiple surgical adverse events, including delayed gastric emptying, prolonged hospital stay, increased costs, and delay in cancer treatment. Particularly in terms of postoperative pancreaticobiliary diseases, EUS-guided therapy has assumed an essential role as a treatment option in cases where traditional methods are difficult to perform. Nevertheless, EUS-guided gastrointestinal procedures are still relatively new, with some clinical failures, and additional prospective clinical trials are warranted.

904 EUS-Guided Treatment of Gastric Varices: A Systematic Review and Meta-Analysis With Indirect Comparison to Endoscopic Therapy

INTRODUCTION: Gastric variceal (GV) bleeding carries a significant mortality in the setting of portal hypertension. Emergency band ligation and/ or transjugular intrahepatic portosystemic shunt is the current recommended treatment. Other treatment options include direct endoscopic (END) glue injection and endoscopic ultrasound (EUS) guided glue and/ or coil injection. The role of EUS in the treatment of GV is not established and remains an active area of investigation. The aim of this study was to describe the performance of EUS in the treatment of GV. METHODS: We conducted a comprehensive search of several databases (inception to Dec 2018) to identify studies that evaluated END-glue and EUS in the treatment of GV. Our goals were to estimate the pooled rates of treatment efficacy, GV obliteration, GV recurrence, early re-bleeding, late re-bleeding and adverse events with EUS guided therapy in GV. The pooled outcomes of END-glue was used as a comparator group. RESULTS: Total of 35 studies (2777 patients) were included. Mean age range was between 40 and 65 years, with 68% males. N-butyl-2-cyanoacrylate was the most commonly used glue. Use of lipiodol varied among the studies. 28% had GOV1, 48% had GOV2, and 24% had IGV1 (Sarin classification of GV). 63% of the patients had cirrhosis. 30% were due to alcohol and 31% due to viral hepatitis. 11% of the included patients had concomitant hepatocellular carcinoma. GV obliteration with EUS-guided therapy was 84.7% (95% CI 66.8-93.8, I2 = 84.2), and with END-glue was 57.1% (38.2-74.1, I2 = 94.3), P = 0.03. GV recurrence with EUS was 6.1% (95% CI 2.6-13.7, I2 = 51.4, and with END-glue was 22.6% (13.8-34.9, I2 = 77.1), P = 0.006. Late re-bleeding with EUS was 10.6% (95% CI 6.3-17.3, I2 = 45.7), and with END-glue was 20% (14.7-26.6, I2 = 89.30), P = 0.03. The pooled rates of immediate treatment efficacy and early re-bleeding were comparable. On subgroup analysis, EUS-coil/glue combination showed superior outcomes when compared to END-glue (Table 1). The pooled rate of overall adverse events with EUS-glue was 16.5% (9.7-26.9). The rates of adverse event subtypes, and how it compared to END-glue is given in Table 2. CONCLUSION: Based on our meta-analysis, EUS-guided therapies seems to demonstrate benefit in terms of GV obliteration, GV recurrence and late GV re-bleeding. They were significantly superior when indirectly compared to END therapy. The immediate treatment efficacy and early re-bleeding rates were comparable. EUS-coil/glue, in particular, seems to be the best modality.

Combination therapy versus monotherapy for EUS-guided management of gastric varices: A systematic review and meta-analysis.

Cyanoacrylate (CYA), coil embolization, and/or combination thereof are available EUS-guided therapies for the treatment of gastric varices (GV). The primary aim of this study was to perform a structured systematic review and meta-analysis to evaluate the comparative effectiveness of EUS-guided interventions for the treatment of GV. Individualized search strategies were developed for PubMed, EMBASE, and Cochrane Library databases, from inception through November 2018 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This cumulative meta-analysis was performed using calculating pooled proportions. Measured outcomes included technical success, clinical success, adverse events, and rate of rebleeding or reintervention. Comparative subgroup analyses were performed for three treatment cohorts (EUS-guided CYA injection, EUS-guided coil embolization + CYA injection, and EUS-guided coil injection alone). Heterogeneity was assessed with I2 statistics. Eleven studies (n = 536 patients; 62.20% of males) were included. The mean age was 58.21 ± 4.15 years with an average follow-up of 12.93 ± 7.69 months. Overall technical success, clinical success, and adverse events for EUS treatments was 100% ([95% confidence interval [CI] 98–100]; I2 = 30.54%), 97% ([95% CI 92–100]; I2 = 59.99%), and 14% ([95% CI 6–23]; I2 = 82.23%), respectively. On subgroup analysis, EUS-guided CYA + coil embolization resulted in a better technical and clinical success compared to CYA alone (100% vs. 97%; P < 0.001 and 98% vs. 96%; P < 0.001) and coil embolization alone (99% vs. 97%; P < 0.001 and 96% vs. 90%; P < 0.001). CYA + coil embolization also resulted in lower adverse event rates compared to CYA alone (10% vs. 21%; P < 0.001), and comparable rates to coil embolization alone (10% vs. 3%; P = 0.057). EUS-guided treatment overall appears to be an effective and safe modality for GV. Among a variety of EUS-therapies available, EUS combination therapy with coil embolization + CYA injection appears to be a preferred strategy for the treatment of GV over EUS-based monotherapy.

Endoscopic Ultrasound-Guided Vascular Therapy: The Present and the Future.

Endoscopic ultrasound (EUS) offers access to many intra-abdominal vessels that until now have only been accessible to the surgeon and interventional radiologist. In addition to assisting with diagnostics, this unique access offers the potential for therapeutic intervention for a host of indications. To date, this has had the most clinical impact in the treatment of gastroesophageal varices, with EUS-guided coil and glue application growing in use worldwide. Although randomised controlled trial data is lacking, we discuss the growing body of literature behind EUS-guided therapy in the management of varices. EUS has also been used in specialized centres to assist in non-variceal gastrointestinal bleeding. The treatment of bleeding from Dieulafoy lesions, tumours and pancreatic pseudoaneurysms has all been described. The potential applications of EUS have also extended to the placement of portal vein stents and porto-systemic shunts in animal models. As medicine continues to move to increasingly less invasive interventions, EUS-guided therapies offer substantial promise for the safe and effective delivery of targeted treatment for a widening array of vascular disorders.

Advances in endoscopic ultrasound imaging of colorectal diseases.

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-guided therapies in pancreatic neoplasms.

Endoscopic ultrasound (EUS) has evolved from being primarily a diagnostic modality into an interventional endoscopic tool for the management of both benign and malignant gastrointestinal illnesses. EUS-guided therapy has garnered particular interest as a minimally invasive approach for the treatment of pancreatic cancer, a disease often complicated by its aggressive course and poor survival. The potential advantage of an EUS-guided approach revolves around real-time imaging for targeted therapy of a difficult to reach organ. In this review, we focus on EUS-guided therapies for pancreatic neoplasms.

New developments in endoscopic ultrasound-guided therapies.

Endoscopic ultrasound (EUS) has opened new horizons in minimally invasive therapies for diverse gastrointestinal pathologies. Digestive Disease Weak 2015 held in Washington, DC., USA featured exciting research articles on EUS-guided therapeutic procedures. EUS-guided biliary drainage has been attempted and described for many years. There seems to be a lot of interest among various international groups to compare this technique with other alternatives in terms of efficacy and safety. Similarly, EUS-guided pancreatic drainage of cysts and fluid collections continues to evolve with new stents and devices being developed specifically for deployment under endosonographic guidance. EUS-guided ablation of cystic pancreatic tumors is innovative but not always effective. Combining alcohol ablation with injecting chemotherapeutic agents may improve long-term results regarding efficacy. Similarly, for solid pancreatic tumors there appears to be ongoing interest and continuing efforts in injecting different chemotherapeutic or ablative agents, delivering fiducials for radiation guidance and even attempting ablation with radiofrequency. Gastric variceal treatment and EUS-guided anastomoses also continue to be investigated. This review article is focused on the recent developments in EUS-guided therapies presented at Digestive Disease Week (DDW) 2015.

Endoscopic Ultrasound-Guided Treatment beyond Drainage: Hemostasis, Anastomosis, and Others.

Since the introduction of endoscopic ultrasound (EUS) in the 1990s, it has evolved from a primarily diagnostic modality into an instrument that can be used in various therapeutic interventions. EUS-guided fine-needle injection was initially described for celiac plexus neurolysis. By using the fundamentals of this method, drainage techniques emerged for the biliary and pancreatic ducts, fluid collections, and abscesses. More recently, EUS has been used for ablative techniques and injection therapies for patients with for gastrointestinal malignancies. As the search for minimally invasive techniques continued, EUS-guided hemostasis methods have also been described. The technical advances in EUS-guided therapies may appear to be limitless; however, in many instances, these procedures have been described only in small case series. More data are required to determine the efficacy and safety of these techniques, and new accessories will be needed to facilitate their implementation into practice.

Therapeutic Endoscopic Ultrasonography

The development of linear sectorial array EUS scopes in the early 1990s brought a new approach to diagnostic and therapeutic dimensions on EUS capabilities, opening the possibility to perform punction over direct EUS guidance. Endoscopic ultrasound (EUS) has evolved from a purely diagnostic imaging modality to an interventional procedure that provides a minimally invasive alternative to interventional radiologic and surgical techniques. This evolution was catalyzed by the introduction of linear echoendoscopes that provide continuous imaging and observation of needles and by therapeutic devices that pass through large-caliber working channels. The spectrum of EUS-guided interventions is today quite large including drainage of the pancreas, gallbladder, and other fluid collections; access to the pancreatic and biliary systems; celiac plexus interventions; vascular and ablative therapies. Some new indications for interventional and therapeutic endoscopic procedures performed under EUS control have been developed in areas that have been purely surgical for many years. Indications, procedures, and related tools for EUS-guided endosurgery are described, all of which are experimental but may open a new corridor for endoscopists to enter a variety of transluminal procedures in real time without soiling the peritoneal or mediastinal cavity. In this current issue, the readers can have emerging technologies applied to the endoluminal interventions made by using EUS view and another endoscopic resources. On the other hand, the procedures in the therapeutic EUS give us the possibility of having new access through the gastrointestinal wall to closed organs. Beside new EUS-guided therapies, other authors in this collection have made a thorough review of the therapeutic capabilities of EUS. The application of EUS-guided therapy is especially appealing in oncological diseases, offering accurate and effective palliative treatment. This is possible mainly due to two EUS characteristics which are: firstly, its ability to deliver direct treatment to lesions unreachable by other means and secondly, the minimal invasiveness of EUS which allows outstanding results with low complication rate. EUS-guided vascular therapy is a new promising field, because the variety of vascular pathology and the proximity of the vascular structures to the GI tract walls call for EUS-guided vascular procedures. Some reports have suggested that EUS-guided vascular procedure might offer benefits for refractory bleeding, and further development of this technique could potentially replace the interventional radiology in the abdominal vessels. A paper in this issue describes the literature review about EUS-guided vascular procedures, such as EUS-guided management of nonvariceal upper GI bleeding, and EUS-guided management of pseudoaneurysms, giving the reader a quick overview of the current state of research of EUS-guided vascular interventions. Pancreatic cancer is a significant cause of morbidity and mortality. Current therapies, however, are of limited benefit in most patients. Recently, several studies have shown initial success with injection of various medications and therapies into pancreatic tumors under the EUS guidance. This issue carries articles on EUS-guided injection of AdV-tk into the pancreatic tumor, which provide the ability to treat pancreatic cancer in a relatively minimally invasive manner, with a very low incidence of procedural-related complications. The latest cutting-edge technique might provide hope in treating the lethal disease in the foreseeable future. In the articles included in this issue, the reader can find new endoscopic approaches by means of EUS to clinical problems or even complications derived from endoscopic maneuvers. These new technical solutions represent one step ahead in therapeutic endosonography. The clinical benefit and safety profile of some of these approaches must be confirmed in new studies, but they open new fields for clinical and experimental research. The minimal invasive concept is an appropriate nomination to the therapeutic procedures that have been made by endoscopy. The endoscopic ultrasound offers to the endoscopy area a new technological eye to reach nonanatomic trajects creating fistulas or determining cytoreduction of masses. Otherwise, therapeutic endoscopic ultrasound or T-EUS is a new tool to those patients who are not operative candidates and in which we can offer a high quality of life (QOL) during a short survival. Everson L. A. Artifon Marc Giovannini Siyu Sun Juan J. Vila

Esophageal endoscopic ultrasound fine-needle aspiration as a diagnostic tool

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) may be employed for procurement of a tissue diagnosis in a minimally invasive fashion. In many cases, EUS-FNA excludes the need for more invasive diagnostic procedures when a tissue diagnosis is required. In patients with esophageal neoplasms, EUS-FNA is a safe and accurate tool for the preoperative diagnosis of metastatic spread to the paraesophageal and celiac lymph nodes. EUS-FNA is also increasingly recognized as an accurate, cost-effective and safe means of evaluating and staging patients with lung cancer. EUS-FNA is useful in providing tissue confirmation of cancer in cases in which bronchoscopy or computed tomography-guided approaches has been non-diagnostic. EUS-guided therapies are paving the way for therapeutic/interventional EUS. The interventional endoscopist will now play a more central role in the diagnosis and treatment of various gastrointestinal malignancies by delivering antitumor agents.

Interventional Gastroenterology: Esophageal and Pancreatic Cancers

The development and refinement of endoscopic procedures have greatly improved the diagnosis and management of esophageal and pancreatic cancers. Endoscopic ultrasound (EUS) is a highly accurate technique for TNM staging in esophageal cancer, and allows a tissue diagnosis of lymph nodes via fine-needle aspiration with low risk of complications. Endoscopic mucosal resection is a treatment option in patients with early esophageal cancer who are poor surgical candidates. Similarly, EUS fine-needle aspiration is helpful in establishing a diagnosis in cystic lesions, exocrine tumors, neuroendocrine tumors, and other lesions in the pancreas. Endoscopic retrograde cholangiopancreatography provides diagnostic and therapeutic modalities for various pancreaticobiliary problems. A number of promising EUS-guided therapies for pancreatic cancers are under investigation.