Embolization Therapy: Principles and Clinical Applications, 1 Ed.

Balloon-Occluded Retrograde Transvenous Obliteration

Luke R. Wilkins • Wael E. Saad

Gastric and esophageal varices can have multiple etiologies. Most (90%) patients have underlying cirrhosis and portal hypertension. This patient population has a 30% risk of developing varices, with gastric varices representing 10% to 20%. Although the bleeding risk associated with gastric varices is less than that associated with esophageal varices, gastric varices are accompanied with higher rates of morbidity and mortality.1 Treating patients with gastric variceal bleeding necessitates a multidisciplinary team approach, including hepatologists, endoscopists, diagnostic radiologists, and interventional radiologists.1,2

Although upper gastrointestinal (GI) endoscopy is the first-line diagnostic and management tool for upper GI bleeding secondary to varices, endovascular treatment is playing an ever-increasing role in definitive treatment.1,2From the perspective of interventional radiology, there has been a significant amount of controversy regarding the optimal therapeutic management of patients with gastric variceal bleeding.37 Whereas the West (United States and Europe) typically prefers decompression of the portal circulation as the primary treatment approach (i.e., transjugular intrahepatic portosystemic shunt [TIPS]), the East (Japan and South Korea) focuses on the gastric varices themselves, sclerosing them via the balloon-occluded retrograde transvenous obliteration (BRTO) procedure.3,8

Although this chapter will focus on the obliteration (sclerotherapy and/or embolotherapy) of gastric varices, given the complexity and variability of gastric varices, the preprocedural clinical management, endoscopic management, and the preprocedural imaging will also be discussed.

DEVICE/MATERIAL DESCRIPTION

Embolization Agents/Sclerosants

Many agents are available for use in variceal obliteration. Examples include ethanolamine oleate (EO, Oldamin; Grelan Pharmaceutical Co., Ltd., Tokyo, Japan), sodium tetradecyl sulfate (Sotradecol; AngioDynamics, Queensbury, New York), polidocanol foam (Polidocasklerol; ZERIA Pharmaceutical Co., Ltd., Tokyo, Japan), and N-butyl cyanoacrylate. EO is the original agent used for BRTO and remains the agent of choice in Asia.911 Five percent EO is the most common concentration used and is made with 10% EO and the same dose of contrast medium.9,11 EO causes hemolysis with the release of free hemoglobin which may result in renal tubular disturbances and acute renal failure. The administration of 4,000 units of haptoglobin (Green Cross, Osaka, Japan) intravenously will prevent renal insufficiency by binding circulating free hemoglobin. Additional reported complications include pulmonary edema, disseminated intravascular coagulation, and cardiogenic shock.10,12,13 Consequently, some authors recommend limiting EO to a volume of 40 mL per procedure. Routine use of this agent in the United States is markedly limited as haptoglobin is not approved by the U.S. Food and Drug Administration (FDA).

Sodium tetradecyl sulfate (STS) has been extensively used for sclerotherapy of superficial lower extremity varicose veins in both liquid and foam forms.14,15 Additional uses include treatment of venous malformations, male varicoceles, and pelvic congestion syndrome.1619 There are many potential advantages of STS foam, including minimal administered doses, contact with variceal wall, density of material, and efficiency of endothelial damage. A recent study demonstrated a marked decrease in amount of STS given when comparing the liquid mixture (34.1 mL, range 10 to 65 mL) to the foam mixture (10 mL, range 1 to 20 mL). This lower dose may correspond to decreased systemic effects of hemolysis and renal failure without significantly affecting technical success. Further, STS foam is thought to provide improved contact with the variceal wall in comparison to liquid sclerosing agents. This has been demonstrated in the treatment of lower extremity varicose veins where foam sclerotherapy was found to be far more effective than liquid sclerotherapy by improved displacement of the blood volume along with providing a larger surface area of the sclerosant to contact the venous endothelium.15 In vivo studies have demonstrated pathologic damage to the endothelium to be rapid and occur within the first 2 minutes of contact, followed by intimal edema, progressive intimal separation from the tunica media, and microthrombi formation in the following 30 minutes.20 In addition, the foam sclerosants have a tendency to ascend immediately into nondependent gastric varices when compared with more dense liquid sclerosants.

Sotradecol is available in 1% and 3% concentrations. Although a recent study suggested that there is no added benefit in using 3% versus 1% concentration, 3% Sotradecol is often favored as it provides the highest dose possible to the varix.15 Although there is no standard method of foam preparation, it is recommended that 3% Sotradecol be mixed with gas (air or carbon dioxide [CO2]) along with Lipiodol for added visualization in the following ratio: 2 mL STS : 1 mL Lipiodol : 3 mL air/CO2.13 Although many observe that room air remains in foam solution longer than CO2, there remains concern that room air may potentially embolize to the lungs or the systemic circulation via a patent foramen ovale as it comes out of solution.21,22 Alternative sclerosant mixtures include foam EO (10 mL of 10% EO : 10 mL iodinated contrast medium : 20 mL of air) and foam polidocanol (2 mL of 3% polidocanol : 8 mL of air).

With regard to occlusion balloons, there are several options available in the United States and include the Coda (Cook Medical, Inc., Bloomington, Indiana), Python occlusion balloon (Applied Medical, Rancho Santa Margarita, California), Equalizer (Boston Scientific Corporation, Natick, Massachusetts), and flow-directed occlusion balloon catheters (Cook Medical, Inc., Bloomington, Indiana).

Complete details on inventory (sclerosants and catheters) are beyond the scope of this chapter; however, they are discussed in detail by Saad et al.,23 including specifications for balloon occlusion catheters.

TECHNIQUE

Procedural Steps

Access is usually achieved via the right femoral or internal jugular vein using standard angiographic technique and placement of a 6-Fr to 12-Fr sheath. More commonly, access is through a right femoral vein approach. However, some institutions use the jugular vein approach exclusively. Preprocedure imaging may aid in deciding which approach provides the best angle for selecting the shunt.

During a conventional BRTO, the gastrorenal shunt (GRS) is catheterized via the left renal vein using a balloon occlusion catheter (a compliant balloon mounted on a catheter). Balloon occlusion catheters with a reverse curve are available in Asia and provide easier and more stable access into the shunt. These catheters are not readily available in the United States, and it is suggested that stable access into the inferior vena cava (IVC) or distal renal vein be secured with an appropriately sized sheath (6-Fr to 12-Fr). The renal vein may be selected with a 5-Fr diagnostic catheter (Cobra; AngioDynamics, Queensbury, New York). The diagnostic catheter can then be exchanged for an angled-tip catheter, which may be used to select the shunt. Alternatively, a 5-Fr Simmons 2 catheter (AngioDynamics, Queensbury, New York) may be used to select the renal vein and withdrawn until the tip engages the shunt. A 0.035-in stiff guidewire (TAD II [Mallinckrodt Inc., St. Louis, Missouri] or Rosen [AngioDynamics, Queensbury, New York]) is advanced into the shunt as far as possible and the angled-tip catheter is exchanged for an occlusion balloon that is sized to occlude the communicating GRS of interest. The diameter of occlusion balloons ranges from 8.5 to 32 mm. Selection of the proper occlusion balloon would optimally occur at the time of preprocedure imaging (as detailed earlier). A new technique for selection of the shunt from the left renal vein via a femoral approach using a straight reinforced sheath is called the PRESS technique (Pullback RE-inforced Straight Sheath).24,25 The left renal vein is selected with a catheter (usually Cobra-shaped) and a 0.035-in Rosen wire is advanced into the left renal vein into the left renal hilum. The Cobra catheter is exchanged for a reinforced sheath. Pullback venography through the sheath as it is withdrawn over the anchoring Rosen wire is performed. The anchoring wire and the shape of the reinforced sheath allows the sheath to “scrape” the superior aspect of the left renal vein. The sheath will then “pop” into the shunt.24,25

Balloon occlusion venography may then be performed to define the type of varix/varices and the anatomy of the venous drainage. As will be discussed in greater detail in the section entitled “Preprocedure Imaging,” venous drainage patterns may be classified into type A, B, or C (Fig. 32.1). Type D drainage patterns lack a definable shunt and are unable to be treated via the BRTO procedure.5,26

Following balloon occlusion venography, the sclerosant may be infused. The goal of sclerosant infusion is filling of the extent of the varix with the embolization end point of minimal filling of the afferent portal vein branch(s). Although the injection of the sclerosing agent can be performed with or without the use of a microcatheter, it is recommended that a microcatheter be advanced as deeply as possible into the varix and sclerosing agent administered through the microcatheter. This allows the advantage of selective delivery of the sclerosant into the varix while minimizing the amount of volume (optimizing distribution of the sclerosant) used as well as minimizing the risk of balloon rupture when the sclerosant comes in contact with the balloon. Full opacification of gastric varices may be prevented by leaking collateral veins such as the inferior phrenic or paravertebral veins. Occlusion with coils or Gelfoam pledgets (Pfizer, New York, New York) through the microcatheter can help occlude these veins, allowing concentration of the sclerosant at the varix and minimize nontarget efflux of sclerosant into the portal system or systemic vasculature.

Following infusion of chosen sclerosant, the occlusion balloon(s) remain inflated for a minimum of 4 hours and a maximum of 24 hours. Although the balloon(s) may be left in place overnight and deflated under fluoroscopy the following day, this will likely increase access site bleeding, infection rates, and patient inconvenience. Research suggests that there is no observable change in obliteration rate or complication rate when leaving inflated for 4 hours as opposed to 24 hours.13

CLINICAL APPLICATIONS

Preprocedure Evaluation and Management

Clinical Management

A patient presenting with underlying liver disease and upper GI bleeding should be appropriately evaluated and closely monitored. When the patient is clinically stable, upper endoscopy is typically performed for first-line diagnostic and therapeutic purposes.2 It is advised that aggressive volume resuscitation be avoided as variceal bleeding may be exacerbated by fluid overload. After identification of bleeding gastric varices, the management involves diagnostic and therapeutic considerations necessitating a multidisciplinary approach. A management protocol flowchart may be found in Figures 32.2 and 32.3. Although this will briefly be discussed in the following pages, a complete discussion regarding management of gastric varices is outside the scope of this chapter. The reader is referred to the current literature regarding indications and management of gastric varices.27

Endoscopic Evaluation and Treatment

As mentioned earlier, routine upper endoscopy is performed early in the clinical course of a patient presenting with melena or hematemesis. The endoscopic evaluation is essential for identification of which varices (if any) are bleeding in addition to identifying the types of underlying gastric varices. This is usually classified according to the Sarin endoscopic classification (Fig. 32.4). This classification helps to differentiate and triage the bleeding varices so that optimal therapy may be considered. Esophageal varices can often be controlled effectively by endoscopic-guided banding and sclerotherapy. Bleeding esophageal varices that cannot be controlled medically and endoscopically would warrant the creation of a TIPS. If gastric varices are identified on evaluation, then a different endoscopic and endovascular approach is warranted. In addition to etiologic identification, the stigmata of “high-risk gastric varices/impending bleeding” and/or stigmata of recent bleeding may be identified by endoscopy. If high-risk gastric varices with recent bleeding or actively bleeding cardiofundal varix is encountered in the course of that endoscopic evaluation, several clinical avenues may be considered. Conventional endoscopic therapy involves attempts at sclerosants and/or banding. However, studies have demonstrated relatively high failure rates for acute control and early rates of rebleeding.28 Recent comparative trials of sclerotherapy versus banding demonstrate high rebleeding rates of 30% to 45% in both groups, underscoring the significant morbidity associated with such endoscopic methods and enforcing the need for alternative treatment techniques.29 Cyanoacrylate injection may also be considered as a hemostatic agent for gastric variceal bleeding. Although its use in the United States has been limited, several trials have emerged as its use has been established as a primary means of achieving gastric varix obliteration. Although demonstrating improvement when compared with conventional techniques, cyanoacrylate maintains rebleeding rates from 15% to 27%.30,31 The elevated rebleeding rate of both conventional TIPS and endoscopic treatments have only served to increase interest in alternative treatment techniques such as BRTO.

Preprocedure Imaging

Both three-phase contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance angiography/venography (MRA/MRV) may be used for preprocedural evaluation and are equally effective at providing optimal visualization of the main portal vein and its tributaries.2 Advantages of CECT include availability, multiplanar reconstructions, and speed. When protocoling a CECT for BRTO, it is important to not give oral contrast as this may obscure visualization of the varices. Water may be used as it provides gastric distension and acts as a negative contrast agent for the contrast-enhanced gastric varices. In addition, it is recommended that images be acquired from the level of the midchest through the pelvis so as to fully evaluate the extent of existing portosystemic shunts.32Advantages of MRA/MRV include lack of ionizing radiation, decreased nephrotoxicity, and evaluation of portal hemodynamics. It is important that images be acquired in the coronal plane and include dynamic postcontrast sequences. In addition, rapid sequences, such as the vastly undersampled isotropic projection reconstruction (VIPR) sequence (GE Healthcare, Milwaukee, Wisconsin), are promising in evaluating portal hemodynamics.2

Following image acquisition, many variables must be weighed when evaluating a patient for a possible BRTO and technical planning of the procedure. Several anatomic and hemodynamic factors to consider before performing a BRTO include splenic vein (SpV) patency, portal vein patency, and presence and size of the portosystemic shunt. In addition, for unconventional BRTO, one should note the presence and size of alternative portosystemic shunts and leading supradiaphragmatic and infradiaphragmatic systemic veins that can be seen traversing the diaphragm to reach the subphrenic gastric variceal complex. These include the left phrenic, left pericardiac vein, and the azygo-esophago venous/variceal axis (Fig. 32.5).2

Assessing SpV patency allows differentiation between segmental (sentinel) and generalized (global) portal hypertension. This differentiation is critical for the management of gastric varices. Segmental portal hypertension involves thrombosis of the entirety of the SpV in the absence of portal vein thrombosis. Alternatively, segmental portal hypertension may be caused by acute or chronic pancreatitis with focal occlusion of the distal SpV. Generalized portal hypertension may be differentiated by classically showing secondary signs of a hepatic etiology (i.e., cirrhosis). Radiographic signs of portal hypertension include portal vein diameter greater than 14 mm, occasional portal vein thrombosis (partial or complete), cavernous transformation of the portal vein, and the presence of right-sided portosystemic collaterals (e.g., recanalized paraumbilical vein and esophageal varices along the left gastric and hemiazygous venous axis).2

The presence or absence of portal vein thrombosis, although a potential sequelae of a GRS, should also be noted in preprocedural imaging. GRSs and splenorenal shunts are portosystemic collaterals that have hepatofugal flow and may promote hepatofugal flow in the SpV and even the main portal vein. A complex set of hemodynamic variables will determine to the extent that the portal circulation is affected by a GRS, including size of the GRS, presence of TIPS, patency of the main portal vein, resistance of the sinusoidal bed, etc.26,33 As one would imagine, in the presence of main portal vein thrombosis, the GRS will act as a main outflow for the splenic and mesenteric veins. Occlusion of the GRS through a BRTO procedure would potentially cause mesenteric venous hypertension and mesenteric ischemia with possible thrombosis of the entire splanchnic portal venous circulation.2 However, the hemodynamics of the portal circulation is incompletely understood and the risk may be somewhat diminished in the presence of cavernous transformation of the portal vein. These risks should be carefully weighed against any potential benefits before a proposed BRTO.32

Last, for a conventional BRTO procedure, one must assess for the presence of a large infradiaphragmatic (i.e., left-sided) portosystemic collateral/shunt. These shunts include the splenorenal, gastrorenal (combine gastrosplenorenal), gastrocaval, gastrophrenic, and gastrogonadal portosystemic shunts.26 The most common shunt that is found and occluded during a conventional BRTO is a GRS, which provides portal venous outflow to the gastric varices in 90% of patients with gastric varices. The shunts may be classified according to the venous drainage pattern into A, B, C, or D (see Fig. 32.1).12,25 In addition, the diameter of the shunt is usually measured to plan for the BRTO and select for the appropriate equipment. The diameter of the shunt is typically measured at the distal shunt near the renal vein and is frequently the location where the interventional radiologist will attempt to occlude the shunt with the occlusive balloon for the BRTO procedure. It should be noted that the distal shunt may not correspond to the narrowest point of the shunt and it is for this reason that a thorough evaluation throughout the extent of the shunt is warranted. Further, attention must be paid to the presence of venous webs that may cause additional narrowing within the shunt and may aid in occlusion balloon catheter placement. On occasion, the size of a GRS on cross-sectional imaging will preclude a BRTO procedure; however, one may be attempted as computed tomography (CT) and magnetic resonance imaging (MRI) frequently underestimate the presence of webs. Only after cannulation and balloon occlusion can the true diameter and ability to safely occlude the GRS be tested with the balloon occlusion catheter available.

In the absence of a GRS or gastrocaval shunt (required for a conventional BRTO), alternative portosystemic collaterals/routes may be evaluated for the possibility of an unconventional BRTO. These routes may include gastrophrenic, pericardiogastric (left pericardiac vein), and azygous/hemiazygous to left gastric vein axis. Additionally, these routes may be present with a coexisting GRS, which may hinder the BRTO and allow escape of sclerosant into the systemic circulation.

Treatment Modifications According to Draining Venous Pattern

As detailed earlier and outlined in Figure 32.1, shunts may be classified according to the venous drainage pattern into A, B, C, or D.5 Treatment of gastric varices may require modification on the basis of the draining venous pattern.

Type A varices are contiguous with a single draining shunt. This is most commonly a GRS and less commonly a gastrocaval shunt draining through an enlarged inferior phrenic vein directly into the IVC. This type of drainage pattern is the easiest to treat given the absence of leaking collateral veins or additional shunts. Further, the entire varix can be visualized during balloon-occluded retrograde venography. As detailed earlier, the microcatheter can then be advanced through the balloon occlusion catheter as deep as possible into the varix and sclerosant administered to embolization end point of minimal filling of the afferent vein/portal vasculature (Fig. 32.6).34

Type B varices are contiguous with a single shunt (most commonly a GRS) and one or more collateral veins. These collaterals drain through a plexus of vessel back to the right atrium or IVC without formation of a definable shunt. These draining veins may include the pericardiophrenic, ascending lumbar, intercostal, perivertebral, or rarely the azygous. Unlike the type A drainage pattern, full opacification of the varices is not achieved on retrograde venography secondary to preferential flow of contrast into the leaking collateral veins. If the collateral veins are able to be catheterized, then embolization may be performed with coils or Gelfoam pledgets (Fig. 32.7). However, if the veins are unable to be catheterized due to size and/or number, several different treatment strategies exist. The occlusion balloon may be advanced beyond the leaking collateral vessels and repeat venography performed. If this is able to fully opacify the varix without evidence of additional leaking collateral, sclerosant may safely be administered from this location (Fig. 32.8). This technique may be challenging due to shunt tortuosity and balloon catheter maneuverability. This limitation may be overcome by advancing the balloon over the microcatheter as deeply as possible into the varix. Fukuda et al. reported success in 87% of cases using this technique.21 Alternatively, flow-directed embolization of the collaterals may be performed from the shunt using sclerosant, Gelfoam pledgets, or absolute alcohol in a stepwise fashion until repeat venography demonstrates full varix opacification. Last, the microcatheter may be advanced beyond the collateral and repeat venography performed. If this is able to fully opacify the varix without evidence of leaking collateral, the sclerosant may be administered from this location.34

Type C varices are contiguous with both gastrocaval and a gastrorenal shunt. If one of the shunts is small in size and can be catheterized using a microcatheter, the shunt may be coil embolized before sclerosant infusion through the remaining shunt. If the gastrocaval shunt is large enough to be catheterized with an occlusion balloon, then a second occlusion balloon may be advanced via a second access site (e.g., internal jugular). Repeat venography will then show full varix opacification and administration of the sclerosant can be performed (Fig. 32.9).34

Treatment Modification Based on Afferent Vein Anatomy

Gastric varices may also be categorized based on afferent vein anatomy (Fig. 32.10). Type 1 are supplied by a single afferent gastric vein and is most commonly the left or posterior gastric vein. As the outflow vein(s) are appropriately occluded, the sclerosant will reflux into the gastric variceal complex and stagnate secondary to the high pressure from the portal venous circulation. This allows slow minimal reflux into the afferent vein, signaling the critical end point of embolization. Any additional forceful injection can overcome the portal pressures and cause further reflux into the portal system.

Gastric varices are more frequently supplied by multiple afferent gastric veins.34 In type 2, there are two separate afferent veins (left and posterior gastric veins). When the draining vein or veins are appropriately occluded, the sclerosant will stagnate in the gastric varices and minimally reflux into one or both afferent veins. However, the pressure in one of the afferent veins is commonly lower than in the other afferent vein. Reflux will be noted in the lower pressure vein, signaling the end point of embolization, and the procedure is typically completed at that point. This will typically result in only partial obliteration of the varices because the other, higher pressure afferent vein will remain patent and supply a portion of the gastric varices, resulting in the necessity of a second BRTO procedure.34 Preprocedure imaging may or may not identify both afferent veins and, unless both veins have similar pressures so that reflux into both veins is documented on balloon-occluded venography, the typical result is partial obliteration. Given the complication associated with excessive administration of sclerosant and untoward reflux into the portal venous system, it is appropriate to stage the procedure and plan on a repeat BRTO after several weeks to allow the sclerosed afferent vein to thrombose and allow for embolization of the higher pressure afferent vein at the second session.

Type 3 gastric varices have a separate afferent vein that drains directly into the shunt and does not communicate to the gastric varices. During BRTO, this will cause a challenge as sclerosant will typically flow into this separate afferent vein rather than the gastric varices and will cause reflux into the portal venous system.34 It is essential to advance a microcatheter deeply into the gastric varices for a planning venogram to document the ability to achieve stagnation within the varices and reflux into the afferent veins feeding the gastric varices. If this cannot be achieved through the microcatheter, then the separate afferent vein must be embolized by a percutaneous transhepatic or transjugular route to eliminate it from the circuit.

Transjugular Intrahepatic Portosystemic Shunt and Portal Venous Modulators

In the United States, TIPS placement is still more frequently performed for bleeding gastric varices. Although TIPS has been reported as effective in the treatment of bleeding gastric varices, it has higher rates of encephalopathy when compared with endoscopic therapy and BRTO.11,35,36 Further, large gastric varices will frequently continue at lower portal pressures because of the decompressive effect on the portal venous system. In addition, gastric varices are more likely to bleed at lower pressures when compared with esophageal varices.11,13,37 Despite having a functioning TIPS, patients may still have recurrence of gastric variceal bleeding and require alternative treatments such as BRTO.13 Many clinical and anatomic factors must be considered when deciding on treatment of bleeding gastric varices. As such, Saad and Darcy3 have argued for combining BRTO and TIPS for patients with baseline substantial ascites or hydrothorax or uncontrolled esophageal varices who have reasonable hepatic reserve (Model for End-Stage Liver Disease [MELD] score <19). Alternatively, other portal venous modulators such as splenic artery embolization have been found to offset the increasing portal venous pressures after BRTO by the reduced development and bleeding rate of esophageal varices.10 This has been substantiated by a recent study demonstrating superior results for combining BRTO with TIPS compared to BRTO only.38Rebleeding at 6, 12, and 24 months after the procedure(s) for BRTO and TIPS versus BRTO only was 0%, 0%, and 0% compared to 9%, 9%, and 21%, respectively.38

POTENTIAL COMPLICATIONS

Most described complications are often transient and self-limited. When compared with endoscopic N-butyl cyanoacrylate glue injection, BRTO shows similar incidence of complications.39 Epigastric and back pain, fever, and hematuria are most common and found in large percentage of patients.4,4045 Less commonly, nausea, elevated blood pressure, and changes in laboratory values may be present.42,45

There are varying degrees and rates of new or worsened ascites and hydrothorax. Given the resultant elevated portal pressures following a BRTO, this is not unexpected, and some studies show ascites to increase in 44% of patients and worsened hydrothorax in 72% of patients.45 Most of these patients frequently return to baseline a few months after the procedure.46 The incidence of ascites after BRTO at 6, 12, and 24 months after BRTO is 43%, 57%, and 71%, respectively.38 Portal vein and renal vein thrombosis may be found in a small number of patients but is typically clinically silent.13,45 Pulmonary embolism has been a reported complication and can be symptomatic. However, the embolus has not been described as containing high-density material to suggest an origin from treated gastric varices.13,45,47Although rare, potentially life-threatening complications include ventricular fibrillation, pulmonary edema, and anaphylaxis to EO.13,19,45,47 Careful respiratory monitoring is warranted as changes in pulmonary function parameters after BRTO may not be accompanied by clinical symptoms.48 Although not frequently reported as a complication, balloon rupture can occur and may result in antegrade transit of sclerosant into the systemic vasculature.49 Last, the use of foam sclerosant prepared with room air has been associated with air embolism to the lungs or the systemic arterial circulation in the presence of a patent foramen ovale.21,22 This has not been reported with transcatheter variceal obliteration but has been associated with lower extremity vein sclerotherapy. The rate of this complication may theoretically be reduced by the use of CO2 rather than room air.50,51

TIPS AND TRICKS

• Careful evaluation of preprocedural CECT or MRI is very important for preprocedural evaluation and planning. Coronal reformats are the most important and most informative.

• CECT or MRI usually overlook, if not underestimate, vascular weblike narrowings in the GRS, thus estimates of required balloon sizes before the procedure maybe serendipitously overestimated.

• Foam sclerosant (sclerosant is a foam state by mixing the sclerosant with air or CO2) reduces the sclerosant dose-to-volume ratio and is probably safer from a systemic toxicity standpoint.

• The objectives of balloon-occluded retrograde venography are to (1) identify decompressive collaterals (potential escape routes for sclerosant), (2) familiarize the operator with shunt and variceal anatomy, and (3) familiarize the operator with the portal venous feeders.

• The technical end point of the BRTO procedure is to fill the entire gastric variceal system with sclerosant and partly fill/visualize the portal venous feeders.

• If you cannot pass a microcatheter coaxially through the balloon occlusion catheter, the microcatheter can be passed adjacent to the compliant balloon occlusion catheter.

• The ideal feature of a balloon occlusion catheter for BRTO is one that does not have the catheter tip extend beyond the compliant balloon. Moreover, a catheter that invaginates within the balloon is better.

• The negative aspect of the BRTO procedure is that the spontaneous GRS is obliterated as well as the gastric varices.

• The obliteration of the spontaneous GRS (a portosystemic shunt) potentially diverts portal blood flow (which commonly escapes portosystemically) back into the portal circulation, commonly increasing portal flow to the liver and increasing portal pressure.

• Increased portal pressure after BRTO is associated with negative hemodynamic effects such as worsening ascites, esophageal variceal bleeding, and splenomegaly.

• Increased hepatopetal portal blood flow after BRTO is associated with positive hemodynamic effects such as reduction in hepatic encephalopathy and improved synthetic function.

OUTCOMES

Technical success as defined by successful filling of gastric varices with sclerosant is reported to occur in 77% to 100% of patients.52 Complete obliteration of the gastric varices is reported to occur in 82% to 100% of patients. Although some studies required repeat BRTO to achieve such high percentages, large volumes of sclerosants are often required.4,7,11,53 Short and midterm follow-up periods are typically reported in the literature, and reported rebleeding rates are as high as 15%.39 However, most studies report bleeding rates below 5%.46 Long-term rebleeding from gastric varices at 12 and 24 months after BRTO were 0%.38 When compared with endoscopic N-butyl cyanoacrylate injection in a recent prospective study, BRTO demonstrated a significantly higher probability of bleeding-free survival.39 Further, this study showed increased survival rates in patients with transcatheter therapy or rescue transcatheter therapy after failed endoscopic therapy versus endoscopic therapy alone in the acute phase. Additionally, transcatheter obliteration frequently requires fewer treatment sessions, has higher eradication rates, and is associated with shorter hospital stays when compared with endoscopic sclerotherapy.

Given that the purpose of BRTO is to embolize a decompressive shunt, it is not unexpected that 10% to 68% of patients experience worsening esophageal varices. This is more likely to occur when the esophageal varices are present before the BRTO.47,54 These are most often successfully treated endoscopically.45 Further, although shunt embolization may cause an increase in portal pressures and worsening of esophageal varices, it may also cause redirection of portal blood flow toward the liver and result in clinical improvement. Resolution or marked decrease in degree of encephalopathy has been reported.4,53In addition, significant decreases in serum ammonia,40,53improved serum albumin,41,55 resolution of ascites,4 and improved hepatic reserved was reflected by improved Child-Pugh and/or MELD scores.4,40,56

FUTURE DIRECTIONS

The ideal management of a patient with bleeding gastric varices heavily depends on many factors such as patient anatomy, hemodynamic stability, and institutional availability. Furthermore, although BRTO will remain an effective treatment technique in this patient population, the combination of BRTO with portal venous modulating procedures (i.e., TIPS and splenic artery embolization) may be required in a select group of patients.3,8,10 Determining defined parameters for both the clinical and imaging presentation of this patient population is an area of ongoing research. Additional research is being performed on the application of this technique to nontraditional varices such as small bowel varices,5759 spontaneous mesenteric portosystemic shunts,54,60 and parastomal varices.61 BRTO from unconventional venous routes is also being performed in greater numbers.6265 Combined techniques are also being evaluated. For example, a technique has been described that combines endoscopic and percutaneous approaches for balloon-occluded endoscopic injection sclerotherapy.65 This method allows gastric variceal obliteration in patients without large draining veins.

CONCLUSIONS

BRTO is a well-established technique for treating gastric varices. Although the technique was popularized in Asia, it has been slow to be adopted in Western countries. However, the technique is rapidly being incorporated into the management of cirrhotic patients with bleeding gastric varices. Further investigation and research is needed to determine defined clinical and imaging parameters for patients presenting with bleeding gastric varices. In addition, more research into the combination of variceal obliteration with portal vein modulating treatments is needed. Although BRTO may cause aggravation of esophageal varices or exacerbation of transudative complications, the clinical weight of these consequences is yet to be determined. Despite these unknowns, BRTO has become and will remain a key component in the management of patients with bleeding gastric varices.

REFERENCES

 1. Al-Osaimi AMS, Caldwell SH. Medical and endoscopic management of gastric varices. Semin Intervent Radiol. 2011;28:273–282.

 2. Al-Osaimi AMS, Sabri SS, Caldwell SH. Balloon-occluded retrograde transvenous obliteration (BRTO): preprocedural evaluation and imaging. Semin Intervent Radiol. 2011;28:288–295.

 3. Saad WEA, Darcy MD. Transjugular intrahepatic portosystemic shunt (TIPS) versus balloon-occluded retrograde transvenous obliteration (BRTO) for the management of gastric varices. Semin Intervent Radiol. 2011;28:339–349.

 4. Fukuda T, Shozo H, Sugimura K. Long-term results of balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy. J Vasc Interv Radiol. 2001;12:327–336.

 5. Kiyosue H, Mori H, Matsumoto S, et al. Transcatheter obliteration of gastric varices: part 2. Strategy and techniques based on hemodynamic features. Radiographics. 2003;23:921–937.

 6. Ibukuro K, Sugihara T, Tanaka R, et al. Balloon-occluded retrograde transvenous obliteration (BRTO) for a direct shunt between the inferior mesenteric vein and the inferior vena cava in a patient with hepatic encephalopathy. J Vasc Interv Radiol. 2007;18:121–125.

 7. Ninoi T, Nishida N, Kaminou T, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices with gastrorenal shunt: long-term follow-up in 78 patients. AJR Am J Roentgenol. 2005;184:1340–1346.

 8. Saad WE. The history and evolution of balloon-occluded retrograde transvenous obliteration (BRTO): from the United States to Japan and back. Semin Intervent Radiol. 2011;28:283–287.

 9. Roossle M, Siegerstetter V, Olschewski M, et al. How much reduction in portal pressure is necessary to prevent variceal rebleeding? A longitudinal study in 225 patients with transjugular intrahepatic portosystemic shunts. Am J Gastroenterol. 2001;96:3379–3383.

10. Ryan BM, Stockbrugger RW, Ryan JM. A pathophysiologic, gastroenterologic, and radiologic approach to the management of gastric varices. Gastroenterology. 2004;126:1175–1189.

11. Tripathi D, Therapondos G, Jackson E, et al. The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations. Gut. 2002;51:270–274.

12. Kiyosue H, Mori H, Matsumoto S, et al. Transcatheter obliteration of gastric varices. Part 1. Anatomic classification. Radiographics. 2003;23:911–920.

13. Sabri SS, Swee W, Turba UC, et al. Bleeding gastric varices obliteration with balloon-occluded retrograde transvenous obliteration using sodium tetradecyl sulfate foam. J Vasc Interv Radiol. 2011;22:309–316.

14. Demagny A. Comparative study into the efficacy of a sclerosant product in the form of liquid or foam in echo- guided of arches of the long and short saphenous veins. Phlebology. 2002;55:133–137.

15. Coleridge Smith P. Sclerotherapy and foam sclerotherapy for varicose veins. Phlebology. 2009;24:260–269.

16. Gandini R, Chiocchi M, Konda D, et al. Transcatheter foam sclerotherapy of symptomatic female varicocele with sodium-tetradecyl-sulfate foam. Cardiovasc Intervent Radiol. 2008;31:778–784.

17. Gandini R, Konda D, Reale CA, et al. Male varicocele: transcatheter foam sclerotherapy with sodium tetradecyl sulfate—outcome in 244 patients. Radiology. 2008;246:612–618.

18. Tan KT, Kirby J, Rajan DK, et al. Percutaneous sodium tetradecyl sulfate sclerotherapy for peripheral venous vascular malformations: a single-center experience. J Vasc Interv Radiol. 2007;18:343–351.

19. Yamaki T, Nozaki M, Sakurai H, et al. Prospective randomized efficacy of ultrasound-guided foam sclerotherapy compared with ultrasound-guided liquid sclerotherapy in the treatment of symptomatic venous malformations. J Vasc Surg. 2008;47:578–584.

20. Orsini C, Brotto M. Immediate pathologic effects on the vein wall of foam sclerotherapy. Dermatol Surg. 2007;33:1250–1254.

21. Ceulen RP, Sommer A, Vernooy K. Microembolism during foam sclerotherapy of varicose veins. N Engl J Med. 2008;358:1525–1526.

22. Forlee MV, Grouden M, Moore DJ, et al. Stroke after varicose vein foam injection sclerotherapy. J Vasc Surg. 2006;43:162–164.

23. Saad WE, Nicholson D, Koizumi J. Inventory used for balloon-occluded retrograde (BRTO) and antegrade (BATO) transvenous obliteration: sclerosants and balloon occlusion devices. Tech Vasc Interv Radiol. 2012;15:226–240.

24. Saad WE, Kitanosono T, Koizumi J, et al. The conventional balloon-occluded retrograde transvenous obliteration procedure: indications, contraindications, and technical applications. Tech Vasc Interv Radiol. 2013;16:101–151.

25. Saad WE, Simon PO Jr, Rose SC. Balloon-occluded retrograde transvenous obliteration of gastric varices. Cardiovasc Intervent Radiol. 2014;37:299–315.

26. Saad WE. Vascular anatomy and the morphologic and hemodynamic classifications of gastric varices and spontaneous portosystemic shunts relevant to the BRTO procedure. Tech Vasc Interv Radiol. 2013;16:60–100.

27. Saad WEA, Al-Osaimi AM, Caldwell S, et al. ACR Appropriateness Criteria®: Radiologic Management of Gastric Varices. Reston, VA: American College of Radiology; 2012.

28. Sarin SK. Long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience. Gastrointest Endosc. 1997;46:8–14.

29. Jutabha R, Jensen DM, Kovacs TO, et al. Initial results of a prospective study of combination banding & sclerotherapy compared to sclerotherapy alone for bleeding gastric varices. Gastrointest Endosc. 1998;47:AB86

30. Lo GH, Lai KH, Cheng JS, et al. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology. 2001;33:1060–1064.

31. Tan PC, Hou MC, Lin HC, et al. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-Butyl-2-Cyanoacrylate injection versus band ligation. Hepatology. 2006;43:690–697

32. Saad WE, Al-Osaimi A, Caldwell SH. Pre- and post-balloon-occluded retrograde transvenous obliteration clinical evaluation, management, and imaging: indications, management protocols, and follow-up. Tech Vasc Interv Radiol. 2012;15:165–202.

33. Saad WE, Lippert A, Saad NE, et al. Ectopic varices: anatomical classification, hemodynamic classification, and hemodynamic-based management. Tech Vasc Interv Radiol. 2013;16:158–175.

34. Sabri SS, Saad WEA. Balloon-occluded retrograde transvenous obliteration (BRTO): technique and intraprocedural imaging. Semin Intervent Radiol. 2011;28:303–313.

35. Khan S, Tudur Smith C, Williamson P, et al. Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis. Cochrane Database Syst Rev. 2006;(4):CD000553.

36. Azoulay D, Castaing D, Majno P, et al. Salvage transjugular intrahepatic portosystemic shunt for uncontrolled variceal bleeding in patients with decompensated cirrhosis. J Hepatol. 2001;35:590–597.

37. Watanabe K, Kimura K, Matsutani S, et al. Portal hemodynamics in patients with gastric varices: a study in 230 patients with esophageal and/or gastric varices using portal vein catheterization. Gastroenterology. 1988;95:434–440.

38. Saad WE, Wagner CC, Lippert A, et al. Protective value of TIPS against the development of hydrothorax/ascites and upper gastrointestinal bleeding after balloon-occluded retrograde transvenous obliteration (BRTO). Am J Gastroenterol. 2013;108:1612–1619.

39. Hong CH, Kim HJ, Park JH, et al. Treatment of patients with gastric variceal hemorrhage: endoscopic N-butyl-2-cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. 2009;24:372–378.

40. Takuma Y, Nouso K, Makino Y, et al. Prophylactic balloon-occluded retrograde transvenous obliteration for gastric varices in compensated cirrhosis. Clin Gastroenterol Hepatol. 2005;3:1245–1252.

41. Hiraga N, Aikata H, Takaki S, et al. The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration. J Gastroenterol. 2007;42:663–672.

42. Arai H, Abe T, Shimoda R, et al. Emergency balloon-occluded retrograde transvenous obliteration for gastric varices. J Gastroenterol. 2005;40:964–971.

43. Cho SK, Shin SW, Lee IH, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices: outcomes and complications in 49 patients. AJR Am J Roentgenol. 2007;189:1523.

44. Kitamoto M, Imamura M, Kamada K, et al. Balloon-occluded retrograde transvenous obliteration of gastric fundal varices with hemorrhage. AJR Am J Roentgenol. 2002;178:1167–1174.

45. Sonomura T, Sato M, Kishi K, et al. Balloon-occluded retrograde transvenous obliteration for gastric varices: a feasibility study. Cardiovasc Intervent Radiol. 1998;21:27–30.

46. Kanagawa H, Mima S, Kouyama H, et al. Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. 1996;11:51–58.

47. Akahoshi T, Hashizume M, Tomikawa M, et al. Long-term results of balloon-occluded retrograde transvenous obliteration for gastric variceal bleeding and risky gastric varices: a 10-year experience. J Gastroenterol Hepatol. 2008;23:1702–1709.

48. Arai H, Abe T, Takayama H, et al. Respiratory effects of balloon occluded retrograde transvenous obliteration of gastric varices: a prospective controlled study. J Gastroenterol Hepatol. 2011;26:1389–1394.

49. Park SJ, Chung JW, Kim HC, et al. The prevalence, risk factors, and clinical outcome of balloon rupture in balloon-occluded retrograde transvenous obliteration of gastric varices. J Vasc Interv Radiol. 2010;21:503–507.

50. Morrison N, Neuhardt DL, Rogers CR, et al. Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation. J Vasc Surg. 2008;47:830–836.

51. Peterson JD, Goldman MP. An investigation into the influence of various gases and concentrations of sclerosants on foam stability. Dermatol Surg. 2011;37:12–17.

52. Patel A, Fischman AM, Saad WE. Balloon-occluded retrograde transvenous obliteration of gastric varices. AJR Am J Roentgenol. 2012;199(4):721–729.

53. Hirota S, Matsumoto S, Tomita M, et al. Retrograde transvenous obliteration of gastric varices. Radiology. 1999;211:349–356.

54. Minamiguchi H, Kawai N, Sato M, et al. Balloon occlusion retrograde transvenous obliteration for inferior mesenteric vein-systemic shunt. J Vasc Interv Radiol. 2011;22:1039–1044.

55. Hirota S, Kobayashi K, Maeda H, et al. Balloon-occluded retrograde transvenous obliteration for portal hypertension. Radiat Med. 2006;24:315–320.

56. Saad WE, Wagner CC, Al-Osaimi A, et al. The effect of balloon-occluded transvenous obliteration of gastric varices and gastrorenal shunts on the hepatic synthetic function: a comparison between Child-Pugh and model for end-stage liver disease scores. Vasc Endovascular Surg. 2013;47:281–287.

57. Tsurusaki M, Sugimoto K, Matsumoto S, et al. Bleeding duodenal varices successfully treated with balloon-occluded retrograde transvenous obliteration (B-RTO) assisted by CT during arterial portography. Cardiovasc Intervent Radiol. 2006;29:1148–1151.

58. Zamora CA, Sugimoto K, Tsurusaki M, et al. Endovascular obliteration of bleeding duodenal varices in patients with liver cirrhosis. Eur Radiol. 2006;16:73–79.

59. Hashimoto N, Akahoshi T, Yoshida D, et al. The efficacy of balloon-occluded retrograde transvenous obliteration on small intestinal variceal bleeding. Surgery. 2010;148:145–150.

60. Hayashi S, Baba Y, Senokuchi T, et al. Successful portal-systemic shunt occlusion of a direct shunt between the inferior mesenteric vein and inferior vena cava with balloon-occluded retrograde transvenous obliteration following recanalization after placing a covered stent in the portal and superior mesenteric veins. Jpn J Radiol. 2009;27:180–184.

61. Minami S, Okada K, Matsuo M, et al. Treatment of bleeding stomal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol. 2007;42:91–95.

62. Araki T, Hori M, Motosugi U, et al. Can balloon-occluded retrograde transvenous obliteration be performed for gastric varices without gastrorenal shunts? J Vasc Interv Radiol. 2010;21:663–670.

63. Kageyama K, Nishida N, Matsui H, et al. Successful balloon-occluded retrograde transvenous obliteration for gastric varix mainly draining into the pericardiophrenic vein. Cardiovasc Intervent Radiol. 2012;35:180–183.

64. Minamiguchi H, Kawai N, Sato M, et al. Balloon-occluded retrograde transvenous obliteration for gastric varices via the intercostal vein. World J Radiol. 2012;28:121–125.

65. Shiba M, Higuchi K, Nakamura K, et al. Efficacy and safety of balloon-occluded endoscopic injection sclerotherapy as a prophylactic treatment for high-risk gastric fundal varices: a prospective, randomized, comparative clinical trial. Gastrointest Endosc. 2002;56:522–528.