Endoscopic ultrasonography-guided vascular interventions

Endoscopic ultrasonography-guided variceal obliteration

Tissue adhesives (glues), coils, or a combination thereof may be delivered intravascularly with EUS guidance to obliterate varices. EUS-guided therapy has been predominantly reported as a method of treatment of or prophylaxis against gastric variceal bleeding, though the technique may be employed for ectopic varices, rectal varices, perianastomotic varices, refractory esophageal varices, or in cases of refractory nonvariceal bleeding.

While gastric varices contiguous with esophageal varices along the lesser curvature of the stomach (GOV1 varices) may be managed with endoscopic variceal ligation (EVL), other gastric varix types will usually require differentiated management. This applies particularly to isolated gastric varices (IGVs), which arise in the submucosa. The thicker overlying mucosa found in the stomach, combined with the larger size of IGVs, may result in incomplete entrapment of the varix during attempted band ligation. With incomplete capture of the deeper, larger gastric varix, thrombotic obliteration of luminal flow may not occur, risking severe hemorrhage due to postligation ulceration and sloughing. ^, Thus, instead of EVL, glue injection should be pursued, which is the current standard of endoscopic therapy for IGVs worldwide.

Endoscopic injection of bleeding gastric varices with n-2-butyl-cyanoacrylate was first reported by Soehendra and colleagues in 1986. In 2013, a prospective comparison of n-butyl 2-cyanoacrylate injection versus EVL for the treatment of acute gastric variceal bleeding showed high success for both techniques in initial hemostasis but significantly higher rates of rebleeding following EVL compared to cyanoacrylate (72% vs 32%, P = .03) and a shorter time to rebleeding ( P = .006). Multiple subsequent randomized controlled trials have confirmed the superiority of cyanoacrylate injection; a meta-analysis comparing cyanoacrylate injection to other endoscopic intervention showed equivalent hemostasis rates as well as similar rates of bleeding-related mortality, and complications, but significantly higher rebleeding following EVL therapy.

The use of endoscopic ultrasound carries several advantages over direct endoscopy in the management of gastric varices. Gastric varices are often missed during direct endoscopic examination, since they reside deeper in the gastric wall. In fact, endosonography increases the gastric variceal detection rate sixfold in patients with cirrhosis (79% vs 12.5%). In cases of massive gastric variceal bleeding, EUS permits successful treatment when ongoing active hemorrhage or the presence of large clots would otherwise prevent direct endoscopic identification and targeting of the culprit varix. EUS also enables precise visualization of a feeder vessel, which may promote complete obliteration of a variceal complex with a smaller amount of glue, potentially decreasing the risk of embolization. Doppler assessment during endosonography also allows confirmation of complete obliteration of variceal blood flow, thereby reducing the risk of rebleeding. Additional information gathered at the time of EUS-guided therapy also may help guide salvage therapy. Identification and characterization of portal vein and splenic vein thrombosis helps determine candidacy for interventional radiology-guided TIPS versus balloon-occluded retrograde transvenous obliteration.

In addition, EUS guidance has enabled concomitant deployment of coils along with glue during gastric variceal therapy, with mitigation against potentially catastrophic systemic embolic complications as the primary motivator. Binmoeller and colleagues demonstrated ex vivo that a coil deployed into a container of heparinized blood served as a scaffolding for glue polymerization and fixation ( Fig. 27.1 ). Subsequently, they pioneered this combined injection technique in humans, first reporting use of EUS-guided glue-coil therapy in a case of massive gastric variceal bleeding refractory to conventional cyanoacrylate injection.

Procedural technique

EUS-guided glue-coil obliteration of gastric fundus varices is performed ( Video 27.1 ) as follows. EUS-guided glue-coil obliteration of other bleeding vessels is performed in similar fashion using steps 3 through 11.

• 1.

  With the echoendoscope positioned in the upper stomach, gas is aspirated, and water is infused into the gastric fundus to establish acoustic coupling with the gastric wall ( Fig. 27.2 A). Water filling of the fundus helps differentiate vessels (varices) located in the gastric wall from vessels (collaterals and shunts) located outside the gastric wall. If the patient is not intubated, the head of the bed is elevated to mitigate any risk of aspiration.

  

• 2.

  If possible, the penetrating feeder vessels of a gastric variceal complex are identified for targeting. This usually requires withdrawal of the echoendoscope to the distal esophagus for a transesophageal view of fundal varices. The crus muscle is visualized sandwiched between the esophageal and fundic walls.

• 3.

  Coil diameter size and associated needle size are selected based upon the axial diameter of the target vessel. A 22-gauge fine-needle aspiration (FNA) needle will accommodate up to a 10-mm coil. Larger coil diameter sizes (e.g., 12 mm, 14 mm, 15 mm) require a 19-gauge FNA needle.

• 4.

  The vessel is punctured under EUS guidance. Aspiration of blood is performed to confirm intravascular location of the needle tip.

• 5.

  The needle is flushed clear of blood using sterile water. Intravascular needle position is confirmed by endosonographic visualization of bubbles flowing through the vessel lumen during water injection.

• 6.

  The coil delivery sheath is Luer-locked onto the hub of the FNA needle. The coil is advanced into the needle using a stylet. Once inside the FNA needle, the delivery sheath and stylet are removed, and the stylet reinserted. The coil can be advanced rapidly with the stylet until it is seen to clear the tip of the needle inside the varix. Slow advancement of the coil into the varix is important to avoid backward displacement of the needle out of the vessel into intramural tissue or back into the GI lumen, particularly when a small vessel is being treated ( Fig. 27.2 B).

• 7.

  Aspiration through the needle is again performed to ensure the needle tip remains within the varix lumen following coil deployment. The needle is flushed clear of blood again, observing flow of bubbles through the vessel lumen to again confirm persistent positioning within the vessel. The choice of sterile water or saline for flushing will depend upon whether n-butyl-2-cyanoacrylate or 2-octyl-cyanoacrylate, respectively, is used for varix obliteration. In the case of n-butyl-2-cyanoacrylate, blood or saline within the needle will cause premature hardening.

• 8.

  Cyanoacrylate injection is performed in small aliquots of 0.5 to 1 mL. 2-Octyl-cyanoacryalte is injected slowly over 45 to 60 seconds, whereas n-butyl-2-cyanoacrylate is injected rapidly. EUS visualization shows hyperechogenic shadowing material occluding the lumen.

• 9.

  After complete glue injection, the needle is flushed with at least 1 mL of sterile water to clear all glue from the needle lumen. The needle is withdrawn into the needle sheath. To protect the echoendoscope tip and working channel from contact with residual glue, the needle sheath is extended 2 to 3 cm out of the working channel and the echoendoscope is then removed from the patient with the needle fully retracted within the sheath.

• 10.

  Obliteration of target vessel flow is confirmed by endosonography with Doppler assessment ( Fig. 27.2 C). Residual flow or separate variceal complexes are treated as necessary with additional coil and glue deployment.

• 11.

  Repeat endoscopic examination is performed to ensure no residual active bleeding is present ( Fig. 27.2 D ) . An obliterated varix will be hard under instrumental “palpation.”

Technical and treatment outcomes

Binmoeller and colleagues reported a series of 30 patients who were poor TIPS candidates being treated with EUS-guided glue-coil obliteration for treatment of active or recently (within <1 week) bleeding large gastric varices. One-hundred-percent therapeutic success was achieved, and no procedure-related complications occurred. Surveillance endoscopy ( n = 24) showed complete gastric variceal obliteration with no vascular flow on color Doppler analysis in 95.8% of patients following the initial therapeutic session. One patient was treated with additional EUS-guided coil and cyanoacrylate injection for recurrent gastric variceal bleeding 21 days following initial treatment.

In the largest series to date, 152 patients at our center received EUS-guided glue-coil therapy of gastric varices for treatment of active bleeding (5%), recent bleeding (69%), or primary prophylaxis (26%). Ninety-nine percent therapeutic success was achieved via transesophageal-transcrural or transgastric approach. One technical failure mandated referral for emergent TIPS due to persistent bleeding despite varix injection with a 15-mm diameter coil and 6 mL of 2-octyl cyanoacrylate. A total of 100 out of 152 patients had surveillance EUS with complete gastric variceal obliteration achieved in 93% with a mean follow-up of 436 days. Obliteration was present in most cases following a single session (79%), but required up to three to four sessions in 4% of patients. Rebleeding from gastric varices after initial obliteration occurred in only 3% of patients during follow-up, happening on average at 146 weeks following initial therapy. While eventual coil extrusion into the gastrointestinal lumen is anticipated, extrusion with associated minor delayed bleeding occurred in 3%. In addition, 3% of patients had mild postprocedure pain. One patient had pulmonary embolism, managed with anticoagulation, presenting 1 week after treatment. Overall, the rate of symptomatic embolism of 0.7% (1/152) appeared markedly lower than the rate published for EUS-guided cyanoacrylate injection alone (2/19; 10.5%).

Most recently, a series of 80 patients at our center showed EUS-guided glue-coil therapy is an effective therapy for primary prophylaxis against gastric variceal bleeding, with 100% technical procedural success achieved during treatment of gastric varices with a mean complex size of 22.5 mm. A very high rate of successful gastric variceal obliteration was achieved (96.7%), most often in a single session (71.7%). The need for TIPS was avoided entirely during a mean follow-up period of 3 years. Rebleeding from gastric varices only occurred in 2.5% of patients. Two of 80 patients required 1-day hospitalization for postprocedure abdominal pain, and 2 patients developed pulmonary embolism, managed medically, within 2 weeks of treatment, one attributed to embolization from a preexisting known deep vein thrombus, the other attributed to glue embolization.

A systematic review and meta-analysis comparing combination of EUS-guided coil and cyanoacrylate injection to monotherapy (EUS-guided coil or cyanoacrylate injection alone) examined 11 studies involving 536 patients. This showed EUS-guided glue-coil results in higher technical and clinical success compared to coil therapy or cyanoacrylate injection alone. Combination therapy resulted in similar adverse event rates compared to coil therapy, but lower adverse event rates compared to cyanoacrylate injection alone (10% vs 21%, P < .001).

Technical limitations and complications

Maneuvering the echoendoscope to endoscopically visualize and access gastric varices in the fundus can be challenging, but endosonography-guided therapy can be performed without endoscopic visualization. With the echoendoscope transducer in the distal esophagus, the gastric fundus can be well visualized. The diaphragmatic crus muscle may also be interposed between the esophageal and gastric walls. Thus, gastric variceal therapy may be performed with a transesophageal-transcrural approach with the echoendoscope in an orthograde position. Apart from easier scope positioning, this approach permits variceal therapy without disruption of the typically thinned gastric mucosa overlying the target varix and thereby avoiding “back-bleeding” after puncture. Puncture through the ∼1 cm thick fibromuscular band of the crus muscle also stabilizes the needle within the varix during glue and coil deployment.

Premature glue solidification can result in entrapment of a needle within a varix. Needle puncture of the varix without successful adhesive delivery risks precipitating active bleeding. The primary concern following adhesive delivery is the risk of inadvertent distant vascular embolization, particularly pulmonary embolism, though paradoxical embolic events may also occur including cerebral embolism in the setting of a patent foramen ovale. Splenic and renal vein thrombosis and coronary and splenic artery embolism have been reported as well. In addition, sepsis is possible, with the glue embolus acting as an infection nidus. Additional complications can develop due to imprecise adhesive injection in paravariceal space, resulting in fistulae between the stomach and pleura or mediastinum.

Adverse outcomes may occur, in particular, if the procedural technique does not appropriately factor for varying properties of different glue solutions. Though cyanoacrylate rapidly and completely adheres to the synthetic fibers of a coil submerged in heparinized blood ex vivo, vascular flow in vivo may still disperse glue downstream prior to hardening. Thus, knowledge of and attention to different glue polymerization times is critical to minimize the risk of embolization and the risk of premature hardening within the delivery needle. Most studies reporting on the use of cyanoacrylate injection for gastric varices use n-butyl-2-cyanoacrylate, which polymerizes relatively quickly. Dilution of n-butyl-2-cyanoacrylate with lipidiol, apart from making the adhesive solution radio-opaque, will slow polymerization and help to avoid hardening within the needle. Slowing polymerization also reduces the risk of having the needle become stuck within the varix due to rapid hardening. Conversely, overdilution with lipidiol can prolong adhesive hardening resulting in distant embolization. Lipidiol also makes injection harder due to its viscosity.

As an alternative to n-butyl-2-cyanoacryle, 2-octyl cyanoacrylate polymerizes more slowly, reducing premature hardening risk while eliminating the need for lipidiol dilution. Given slower polymerization, however, inappropriate rapid injection is dangerous with the potential to cause distant embolization. When using n-butyl-2-cyanoacrylate, water but not saline is flushed through the needle, since saline accelerates what is already rapid polymerization. For 2-octyl cyanoacrylate, the needle can be flushed with saline.

It is the practice of the authors to use undiluted 2-octyl-
cyanoacrylate for EUS-guided glue-coil therapy. Given the slower polymerization rate, the 2-octyl-cyanoacrylate must be injected over a longer time frame as specified previously. Alternatively, the authors use n-butyl-2-cyanoacrylate with rapid injection under direct endoscopic visualization through a 23-gauge metal hub needle when active bleeding is occurring, and the exact site of varix bleeding is visible. In some cases of recurrent bleeding from multiple, small-diameter (2 to 4 mm in size), diffuse gastric varices, multifocal therapy is also performed under endosonographic visualization through a 19- or 22-gauge FNA needle with the rapidly polymerizing n-butyl-2-cyanoacrylate. With this technique, a new FNA needle is needed for each site of puncture and adhesive delivery.

In cases of suspected gastric variceal bleeding with presence of only small-diameter varices, the authors have experienced that prevention of rebleeding may be achieved with deployment of intravariceal coils alone without concomitant glue injection. With small vessel diameter, there is increased risk of extravascular glue injection, which can lead to false assessment of hemostasis by obscuring the vessel lumen due to shadowing or temporarily compressing the lumen of the target vessel without actually causing intravascular thrombus/obliteration. Previously, 10-mm diameter by 7-cm long coils, delivered through a 22-gauge FNA needle, were favored for exclusive coil therapy of small vessels in these cases. This coil size has been discontinued, however, such that 10-mm diameter by 15-cm coils are now employed, though this is more technically challenging and significant care is necessary to ensure the coil is fully delivered intravascularly.