Endoscopic ultrasound (EUS)-guided therapeutic interventions have expanded over recent years, especially in the field of endovascular therapy. EUS-guided vascular techniques were developed primarily as less invasive alternatives to surgical and radiological interventions. EUS allows precise vascular access and therapy by providing high-resolution, real-time imaging of the abdominal and mediastinal vascular structures from the gastrointestinal (GI) tract. This review provides an overview of current and emerging EUS-guided vascular interventions, including management of variceal and nonvariceal GI bleeding, EUS-guided portal vein (PV) interventions, and EUS-guided cardiac and pulmonary vascular access.

Variceal bleeding

Esophageal varices

Bleeding from esophageal varices is a common and life-threatening complication in patients with portal hypertension, with an annual bleeding rate of 5% to 15% and a 6-week mortality rate of 20%.¹ Endoscopic band ligation is considered the procedure of choice for the eradication of esophageal varices.² However, recurrent bleeding rates of 15% to 65% have been reported due to failure to treat the paraesophageal collaterals and perforating veins feeding the varices.³ Lahoti et al⁴ were the first to describe the use of EUS-guided endoscopic sclerotherapy for the treatment of esophageal varices. EUS-guided injection of the perforating vessels was performed using sodium morrhuate until cessation of flow; complete eradication of the esophageal varices was achieved with a mean of 2.2 sessions. No complications or rebleeding were reported over a 15-month follow-up period. A separate randomized controlled trial compared EUS-guided sclerotherapy with endoscopic sclerotherapy. No statistically significant difference between the two groups was found in the number of sessions required to eradicate the varices or in rebleeding rates.⁵ Further studies are still needed to evaluate the clinical benefits and practical indications of EUS-guided injection of the perforating veins feeding esophageal varices.

Gastric varices

Gastric varices (GVs) may be present in up to 20% of patients with portal hypertension, with a bleeding rate as high as 65% over 2 years. GVs are classified as isolated GVs (IGVs) or gastroesophageal varices (GOVs). IGVs are subclassified based on location in the fundus or the antrum, while GOVs are subclassified by location along the lesser curve or along the fundus.⁶ Endoscopic cyanoacrylate (CYA) injection is considered the treatment of choice for GVs, with hemostasis rates of 58% to 100% and rebleeding rates up to 40%.⁷ However, CYA injection is associated with many complications, including pulmonary embolism, splenic artery embolism, splenic vein thrombosis, renal vein thrombosis, post-injection ulcers, and the needle becoming stuck in the varix during the injection procedure.⁸ EUS-guided injection of GVs can avoid most of these complications by ensuring accurate delivery of the hemostatic agent into the variceal lumen and can also target the perforating feeding vessel. As suggested by Romero-Castro et al⁹ in a small pilot study, this may enable more effective treatment with a smaller amount of CYA, thus reducing the risk of embolization. Vascular coils can be applied using 19-gauge fine needle aspiration (FNA) needles; these coils serve as a scaffold to retain the glue within the varix and reduce the amount of CYA required to obliterate the varix, reducing the risk of systemic embolization.^10,11 In an ongoing study, our group of researchers is comparing the efficacy and safety of EUS-guided CYA injection into the perforating vein versus direct endoscopic injection of CYA in the treatment of high-risk GVs. Preliminary results indicate that fewer sessions and less CYA are required for obliteration of the GVs in the EUS group compared to the direct injection group (Fig. 1).

Figure 1. Endoscopic ultrasound (EUS)-guided cyanoacrylate (CYA) injection into the perforating vein. (A) Endoscopic view of a large fundic varix. (B) The varix was 4.5 cm × 3.7 cm as shown by EUS. (C) Doppler blood flow inside the varix. (D) Identification of the perforator (arrow). (E) Perforator injection using a 19-gauge fine needle aspiration needle. (F) Immediate reduction of the blood flow in the varix after injection of 1 mL CYA.

A meta-analysis and systematic review was conducted to compare EUS-guided coil embolization combined with CYA injection, EUS-guided CYA injection alone, and EUS-guided coil injection alone. Combined EUS-guided CYA and coiling was found to have higher technical and clinical success rates than either coil embolization alone (technical success, 99% vs 97%, P < 0.001; clinical success, 96% vs 90%, P < 0.001) or CYA alone (technical success, 100% vs 97%, P < 0.001; clinical success, 98% vs 96%, P < 0.001). Similarly, a lower rate of adverse events was found for combined EUS-guided CYA and coiling compared to either coil embolization alone (3% vs 10%; P = 0.057) or CYA alone (10% vs 21%; P < 0.001).¹² These data support the consideration of combined EUS-guided coil embolization and CYA injection for the treatment of high-risk GVs. Another technique is EUS-guided thrombin injection, which was described in a case series of eight patients with complete obliteration of GVs in all patients and no procedure-related complications. Although that series showed promising results, further large prospective studies are still needed.¹³

Ectopic varices

Ectopic varices can develop in the duodenum, small bowel, colon, rectum, and bile ducts and account for 1%–5% of all variceal bleeding.¹⁴ Researchers have reported successful management of duodenal and rectal varices via EUS-guided coiling and/or CYA injection.^15–18 Although most published data regarding EUS-guided injection of bleeding ectopic varices are based on case reports or series, EUS-guided treatment is emerging as a valuable option.

Nonvariceal bleeding

Endoscopic treatments for nonvariceal bleeding are well established and include epinephrine injection, thermal therapy, clipping, and band ligation. However, rebleeding or refractory bleeding may occur in up to 15% of cases.¹⁹ EUS-guided treatment can be used in refractory cases, as real-time Doppler imaging can be used to directly visualize target vessels buried in the walls of the GI tract. A literature review of 35 patients who underwent EUS-guided treatment of nonvariceal bleeding showed satisfactory clinical outcomes in 32 of the 35 (91.4%) patients, with recurrent bleeding in only three patients and no reported adverse events during or after the procedure.²⁰

Levy et al²¹ described the use of EUS in a case series of five patients with refractory bleeding caused by Dieulafoy lesion, hemosuccus pancreaticus, GI stromal tumor, or duodenal ulcer after the failure of at least two conventional treatment options. With EUS guidance, CYA or alcohol was injected into the feeding vessel until cessation of blood flow, with no rebleeding reported over a mean follow-up period of 12 months. Law et al²² performed EUS-guided angiotherapy for 17 patients with refractory bleeding caused by Dieulafoy lesions, GI stromal tumors, vascular malformations, duodenal ulcers, polyps, ulcerated esophageal cancer, invasive prostate cancer, pancreatic pseudoaneurysms, and ulceration after Roux-en-Y gastric bypass. EUS-guided injection of CYA, alcohol, epinephrine, and hyaluronate and coil embolization were performed until cessation of blood flow. However, two patients experienced ongoing bleeding and required repeated intervention. In a prospective study, EUS-guided thrombin injection was described for the treatment of pseudoaneurysm. The study included eight patients with symptomatic visceral artery pseudoaneurysm who were unable to undergo angioembolization. Under EUS guidance, a median dose of 400 IU (200–500 IU) of thrombin was injected with 100% technical success. After 6 months, EUS revealed obliterated pseudoaneurysms in seven patients and recurrence in one patient.²³ EUS-guided intervention for pseudoaneurysms was also described in several case reports.^24–26

EUS-guided angiotherapy has been shown to be effective and safe in the management of nonvariceal bleeding when other therapies fail. However, comparative studies with other endoscopic therapies or interventional radiology are still needed.

Portal vein pressure measurement

The portal pressure gradient (PPG) is measured indirectly as the hepatic venous pressure gradient, which correlates poorly with the directly measured portal pressure in presinusoidal portal hypertension in cases of PV thrombosis and non-cirrhotic portal fibrosis.²⁷ EUS can be used to easily identify PV through the duodenal bulb, allowing access with a standard FNA needle. Huang et al²⁸ published the first human study in which the PPG was measured between the PV and the hepatic vein (HV) (or inferior vena cava). The study included 28 patients and involved a 25-gauge needle connected to a novel compact manometer; results showed 100% technical success and no reported complications. The PPG measurement was correlated with clinical and endoscopic parameters of portal hypertension, including the presence of varices (P = 0.0002), portal hypertensive gastropathy (P = 0.007), and thrombocytopenia (P = 0.036). Tsujino et al²⁹ combined EUS-guided liver biopsy and PPG measurement with significantly shorter recovery time for the EUS procedure compared with percutaneous liver biopsy; no complications were reported. These studies showed that EUS-guided PPG measurement is safe and reliable in humans, although further large studies comparing this technique with standard hepatic venous pressure gradient measurement methods are still needed.

Portal vein blood sampling

Circulating tumor cells (CTCs) are shed from a primary tumor and spread via hematogenous systems to distant sites while preserving tumor characteristics. CTCs are promising new biomarkers in cases of solid tumors, especially in pancreatic cancer, and could be utilized for molecular testing, clinical prediction of future hepatic metastasis, and drug sensitivity analyses.³⁰ In a single-center cohort study, blood samples aspirated from PV with a 19-gauge FNA needle under EUS guidance and peripheral blood samples were collected from 18 patients with suspected pancreatobiliary tumors. CTCs were detected in PV samples in all 18 patients (100%), whereas they were detected in peripheral blood samples of only four patients (22.2%).³¹ In another study, PV and peripheral blood samples were collected simultaneously from patients undergoing pancreaticoduodenectomy for presumed periampullary or pancreatic adenocarcinoma without metastatic disease. CTCs were detected in 58% of PV blood samples compared to 40% of peripheral samples (P = 0.0098). Sixty patients were monitored postoperatively with imaging every 3 months for 1 year, and liver metastasis was detected in 11 of 13 patients with high portal CTC count at 6-month follow-up after surgery.³² Unfortunately, the evaluation of CTCs in blood samples is expensive and is available only in a limited number of specialized centers.

Fine needle aspiration of portal vein thrombus

Malignant portal vein thrombus (PVT) is found in up to 44% of patients with hepatocellular carcinoma (HCC), and the nature of the thrombus influences treatment selection. Moreover, malignant PVT does not always exhibit neovascularity, raising the need for FNA to determine the nature of the PVT.³³ EUS-FNA of PVT for the diagnosis of HCC was first described by Lai et al³⁴ in 2004. This was followed by many case reports describing the use of EUS-FNA of PVT in the diagnosis and staging of suspected or confirmed HCC.^35–37 A retrospective study by Rustagi et al³⁸ evaluating the efficacy and safety of EUS-FNA included 17 patients. The procedure involved using 22- and 25-gauge needles for aspiration from a remote malignant thrombus (a vascular thrombus located away from the primary tumor). Malignancy was confirmed after EUS-FNA in 12 patients (70.6%), including five pancreatic adenocarcinomas, two cholangiocarcinomas, two neuroendocrine tumors, one lung cancer, one lymphoma, and one HCC. In a study conducted by our group that included 34 patients with presumed benign PVT as shown by computed tomography (CT), EUS-FNA from PVT was positive for malignancy in three patients (8.8%), of which only one patient was diagnosed with HCC via triphasic abdominal CT and two patients were newly diagnosed with HCC after EUS-FNA (from cirrhotic nodules in one patient and from a small lesion missed on CT in one patient). EUS-FNA was technically feasible in all patients, despite the presence of portal cavernoma or collateral circulation in 16 patients (47.1%, Fig. 2). No major complications arose in any patient. However, mild abdominal pain was observed in four patients (11.76%), and mild self-limited bleeding at the puncture site was observed during endoscopic monitoring in one patient (2.94%).³⁹ We believe that EUS-FNA should be utilized more frequently in the staging of HCC and the diagnosis of the etiology of PVT.

Figure 2. Endoscopic ultrasound fine needle aspiration (EUS-FNA) of a portal vein thrombus (PVT) at two sites. (A) PVT near the liver hilum (arrow). (B) Doppler ultrasound showing minimal blood flow inside the main PVT with multiple collaterals. (C) EUS-FNA from the PVT despite presence of collaterals. (D) PVT near the confluence with the superior mesenteric vein (arrow). (E) Doppler ultrasound showing partial obstruction of blood flow. (F) EUS-FNA from the PVT.

Liver-directed chemotherapy and radiotherapy

Systemic toxicity is a major complication of chemotherapy in patients with diffuse liver metastases. EUS-guided PV injection of drug-eluting microbeads or nanoparticles has been described in animal models, with significantly higher hepatic and lower systemic levels than those achieved by systemic injection.^40,41 These trials are promising indicators of a new modality for the treatment of liver metastases with lower rates of adverse events than systemic chemotherapy and hepatic artery infusion therapy, the latter of which is associated with a high rate of biliary sclerosis.

Portal vein embolization

Percutaneous selective PV embolization is performed in patients with HCC or cholangiocarcinoma before extensive liver resection. Embolization induces atrophy of the embolized liver lobe and compensatory hypertrophy of the non-embolized remnant liver to prevent postoperative hepatic decompensation. EUS-guided selective intrahepatic PV embolization has been described in porcine models using coiling and CYA delivered through a 19-gauge needle; results included success rates of 88.9% and 87.5%, respectively, and coil migration to the liver in one pig.⁴² Further studies are needed to compare the EUS-guided and percutaneous approaches and to evaluate the long-term effects.

Intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunts are frequently utilized to decompress the portal system in patients with recurrent variceal bleeding and refractory ascites. The EUS-guided establishment of an intrahepatic portosystemic shunt was first described by Buscaglia et al⁴³ in a live porcine model. The HV and PV were sequentially punctured under EUS guidance using a 19-gauge needle followed by the advancement of a guidewire through the needle to the PV. The stent was then inserted over the wire with its distal flange in the PV and its proximal flange in the HV; no complications were reported over a 2-week survival period in the two pigs studied. Binmoeller and Shah⁴⁴ used a similar technique to deploy a fully covered lumen-apposing metal stent in a porcine model. Finally, Schulman et al⁴⁵ successfully deployed a lumen-apposing metal stent for the creation of transjugular intrahepatic portosystemic shunts in five pigs. Long-term data, with refinements of devices and tools, are required before these procedures can be implemented in humans.

The proximity of the heart and pulmonary vessels to the esophagus permits easy access by EUS as transesophageal echocardiography, which is routinely performed in many cardiac patients.

EUS-guided puncture of the heart was first described by Fritscher-Ravens et al⁴⁶ in a porcine model using 22- and 19-gauge EUS needles to access the left ventricle, left atrium, coronary arteries, and aortic valve. The procedures performed included contrast injection into the left atrium, ventricle, and coronary arteries; needle biopsy of cardiac muscle; and radiofrequency ablation of the aortic and mitral valves. No arrhythmias were reported during the procedures. Subsequently, EUS-guided FNA of pericardial effusion was performed for two patients and EUS-FNA of an atrial mass for one patient using 22-gauge needles for diagnostic purposes, with no reported adverse events. EUS-guided drainage of a pericardial cyst was described by Larghi et al⁴⁷ with no complications. Romero-Castro et al⁴⁸ described EUS-guided FNA of a pericardial tumor with a 6-mm hematoma at the puncture site. Gornals et al⁴⁹ described the EUS-guided cardiac puncture of a right atrial tumor with no adverse events over the following 3 days. EUS-guided thrombolysis of a pulmonary artery thrombus in an unstable patient was described by Somani et al⁵⁰ using tenecteplase injected via a 25-gauge needle; follow-up EUS showed a reduction in the volume of the thrombus.

The GI tract provides an excellent window to access vascular structures in the abdomen and mediastinum. Although most published data are based on case reports and series (with the exception of GV management), EUS-guided vascular interventions have been shown to be safe and effective, with good clinical and technical success rates and low rates of adverse events. As this field advances, EUS will offer a safer and less invasive approach to various vascular interventions.

None.

No potential conflict of interest relevant to this article was reported.