In recent years, the role of endoscopic ultrasound (EUS) has expanded rapidly into the therapeutic arena. From its origins in diagnostics and tissue acquisition, EUS-guided therapy now offers options in the management of pancreatic fluid collections, difficult pancreaticobiliary access and in the treatment of gastroesophageal varices.

As mentioned, EUS offers unique access to abdominal arterial and venous vasculature that until now has only been accessible to surgeons and/or interventional radiologists. This has had the most clinical impact on the treatment of gastroesophageal varices, where EUS may play a role both in the acute and elective management and can deliver therapy in the form of glue injection, endovascular coil placement or a combination of the two.

While only currently described in animal studies and case series respectively, EUS can facilitate portal pressure measurement and assist in the management of refractory gastrointestinal bleeding.

This article aims to discuss the body of evidence pertaining to the EUS-guided management of varices as well as to explore available evidence regarding other vascular therapies that have yet to be incorporated into or recommended for everyday clinical practice.

Direct endoscopic therapy for both elective and emergent esophageal variceal bleeding is well established and effective. Forward viewing endoscopy outperforms EUS at both the detection and grading of esophageal varices, however EUS has been shown to be efficacious in assessing potential ‘feeding’ veins [1]. The size of such peri-esophageal veins appears to correlate with bleeding risk [2]. Several studies have also confirmed that the ongoing presence of these veins after endoscopic treatment is associated with an increased risk of recurrence [3,4].

Peri-esophageal veins offer a potential therapeutic target for EUS-guided therapy. Lahoti et al. treated 5 patients with the direct injection of sclerosant into perforating esophageal vessels with obliteration of varices in an average of 2.2 treatments [5]. No recurrence of bleeding was reported after 15 months of follow up. De Paulo et al. conducted a randomised, controlled trial comparing standard endoscopic sclerotherapy with EUS-guided sclerotherapy to treat collateral vessels [6]. The authors showed a trend toward delayed recurrence of varices following EUS-guided therapy, however their results did not reach statistical significance. Neither the amount of sclerosant nor sessions required to achieve eradication were significantly different.

EUS-guided treatment of perforating vessels in cases of esophageal variceal bleeding is an attractive option. Further trials demonstrating superiority over standard endoscopic therapy, potentially using cyanoacrylate (CYA) glue injection in place of sclerosant, would be required before it is adopted into any therapeutic algorithm.

The commonest vascular application of EUS is in the diagnosis and treatment of gastric varices. Gastric varices account for 10%–30% of variceal bleeding episodes and are associated with high morbidity and mortality [7]. The bleeding in these patients tends to be severe and between 35%–90% will re-bleed after spontaneous hemostasis [8].

Injection with CYA glue has become the standard of care for both acute bleeding and secondary prophylaxis. CYA injection has been reported to achieve hemostasis in 80%–90% of bleeding cases, with low rates of re-bleeding [9].

Unlike with esophageal varices, the use of EUS offers a clear advantage in the diagnosis of gastric varices [10]. The use of colour Doppler can reliably differentiate gastric varices from other fundal lesions such as gastrointestinal stromal tumours and thickened gastric folds. EUS has also been used to evaluate the response to gluing. Lee et al. retrospectively compared two groups of patients who received endoscopic (forward viewing) glue treatment for bleeding gastric varices [11]. The first group of 47 patients had repeat treatment on demand, whilst the second group of 54 patients had biweekly EUS and glue injection until obliteration of flow was confirmed on EUS. Although early re-bleeding rates were similar, late re-bleeding rates (>48 hours) were significantly lower in the EUS group (19% vs. 45%, p=0.005).

EUS-guided therapy has been described in case reports for variceal bleeding at other anatomical sites. So et al. described the use of an EUS-guided coil to halt massive duodenal variceal bleeding [22]. The use of CYA glue in this scenario has also been described. Rectal varices are common but have a smaller risk of bleeding than their gastroduodenal counterparts. The uses of both EUS-guided CYA injection and combination therapy with EUS-guided coil/CYA for rectal varices have been described [23,24]. EUS has also been used to direct glue into parastomal varices [25]. While there is currently insufficient evidence to recommend EUS-guided treatment as first line in these cases, it has emerged as a viable option for rescue therapy.

Current rescue therapy for refractory gastroesophageal variceal bleeding is the insertion of a TIPSS. EUS offers unique access to intra-abdominal vasculature including the hepatic and portal veins. The creation of an EUS-guided intrahepatic portosystemic shunt was first described in 2009 [26]. Schulman et al. have recently elaborated on this with a case series of EUS-guided intrahepatic portosystemic shunt formation in 5 porcine models with concurrent portal pressure monitoring [27]. They describe accessing the hepatic vein or inferior vena cava (IVC) using a 19 G needle and advancing the needle into the portal vein, taking pressure measurements at each position. They then deployed a lumen-apposing metal stent over a guidewire using fluoroscopic guidance to establish the shunt. They showed excellent technical success and an average procedure time of 43 minutes. In addition, Park et al. described the placement of transhepatic portal vein stents in 6 pigs, using the left intrahepatic portal vein as a point of access [28].

While the above therapies have only being trialled in animal models to date, they provide an exciting glimpse into the future potential for EUS-guided interventions. Endoscopists will have the capacity to choose from multiple EUS-guided therapies in the acute and rescue settings. Whether these therapies will be shown to provide benefit over current approaches provided by interventional radiology remains to be seen.

EUS provides a potential alternative approach to patients with refractory gastrointestinal bleeding who have failed standard treatment with clips, epinephrine and electrosurgical coagulation. At present, EUS-guided therapy for these patients has only been described in case reports and case series. Levy et al. described therapy for a Dieulafoy lesion, gastrointestinal stromal tumor (GIST), duodenal ulcer and hemosuccus pancreaticus in patients who had failed standard endoscopic and interventional radiological intervention [29]. They described the identification of feeder vessels and then injection of CYA or 99% alcohol via EUS using a 22 G needle. They then used Doppler to confirm the absence of blood flow after therapy and reported a 100% success rate with no re-bleeding at 12 months. Gonzalez et al. have reported on the treatment of Dieulafoy lesions, a bleeding pancreatic tumor, a pancreatic pseudoaneurysm, and an intracystic splenic artery pseudoaneursym [30,31]. Thrombin injection via EUS for pancreatic pseudoaneurysm bleeding has also been described [32]. One of the largest series of EUS-guided interventions was reported by Law et al. [33]. They included 17 cases of refractory bleeding where alternative methods of control were not suitable. Combinations of glue, coils, alcohol and epinephrine injection were used to target bleeding lesions using a linear echoendoscope. They reported 88% success over a 12-month follow-up to prevent recurrent bleeding.

Whilst such reports offer an exciting glimpse into future therapies, there remains a lack of data supporting their use compared to standard therapies currently provided by interventional radiologists (conventional angiography with embolization). As such, EUS should only be considered an option in expert centres when all other treatment modalities have been unsuccessful.

The therapeutic applications of EUS continue to expand at a rapid rate. There is now literature, albeit few randomised, controlled trials, supporting the use of EUS-guided therapy (coil plus CYA) for the treatment of gastric varices. Case reports and case series provide insight into the potential of this modality for the treatment of refractory non-variceal bleeding. EUS-guided portal pressure measurement and portosystemic stenting has been performed in animal studies and may allow for improved outcomes with fewer interventions. 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 options for a widening array of vascular disorders.