Endoscopic management of gastric varices

Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

Contents lists available at ScienceDirect

Techniques in Gastrointestinal Endoscopy journal homepage: www.techgiendoscopy.com/locate/tgie

Endoscopic management of gastric varices Frank Weilerta, Kenneth F. Binmoeller, MDb,n a b

Department of Gastroenterology, Waikato Hospital, Hamilton, New Zealand Paul May and Frank Stein Interventional Endoscopy Center, California Pacific Medical Center, San Francisco, California

a r t i c l e in f o

abstract

Article history: Received 28 December 2016 Accepted 24 March 2017

Understanding the basic pathophysiology and anatomy of gastric varices is critical to the appropriate management of acute variceal bleeding. The high morbidity and mortality of gastric variceal bleeding combined with poor response to treatments for esophageal variceal bleeding has demanded a highly differentiated approach. This review focuses on gastric fundal varices for which the most recent Baveno VI consensus guidelines recommend endoscopic cyanoacrylate-based therapy as first-line intervention. We discuss the evolution of endoscopic techniques, not only to achieve effective hemostasis but also to limit inherent risks and complications. Long-term data reveal that low rebleeding rates are feasible when gastric varices are completely obliterated. Both primary and secondary prophylaxis should become part of standard treatment algorithms. & 2017 Elsevier Inc. All rights reserved.

Keywords: Cyanoacrylate Endoscopic ultrasound Obliteration Rebleeding

1. Introduction Gastric varices (GV) are less common than esophageal varices (EV), but are present in up to 20% of patients with portal hypertension. The cumulative risk of bleeding of incidentally detected GV at 1, 3, and 5 years has been reported to be 16%, 36%, and 44%, respectively [1]. The estimated incidence of bleeding from GV in the United States is approximately 7000 cases per year [2]. The mortality from the first variceal bleed is high at 20% within 6 weeks of the index bleed [3].

2. Nonjunctional vs junctional GV The distinction between nonjunctional and junctional GV is important because the anatomy, risk and severity of bleeding, approach to treatment, and response to treatment differ significantly between the 2 varices [4]. The literature does not always make this distinction. Junctional varices are an extension of EV. Nonjunctional varices are usually seen at the fundus, but may occur in other locations, including the cardia. These may or may not be isolated from junctional varices. Junctional and nonjunctional GV differ fundamentally in their anatomy and pathophysiology. The vascular drainage of the gastric

fundus is via the short and posterior gastric veins or via direct anastomoses with retroperitoneal veins. They are often associated with large gastrorenal venous shunts. This is in contrast to junctional varices that arise from left gastric veins, similar to the esophagus. Nonjunctional varices originate from deep submucosal veins, whereas esophageal and junctional varices originate from the lamina propria. The widely adapted Sarin classification [5] for GV appropriately differentiates gastroesophageal junctional varices (GOV) from isolated gastric varices (IGV). However, GOV are differentiated into GOV type 1 and GOV type 2, which can be a source of confusion. GOV1 are limited to the cardia and typically found along the lesser curvature, whereas GOV2 not only are present at the cardia but also do extend toward the gastric fundus. Emphasis of the nonjunctional variceal component is important, as the 2 varices differ in pathophysiology and treatment. IGV in the Sarin classification are differentiated into the following 2 types: IGV1 are located in the fundus, and IGV2 are located at other “sporadic” locations such as the duodenum. It is the authors’ observation that fundal varices often extend to the cardia without the presence of EV and, therefore, should not be mistakenly categorized as GOV2.

3. Noncyanoacrylate treatment of GV 3.1. Sclerotherapy

The author reports no direct financial interests that might pose a conflict of interest in connection with the submitted manuscript. n Corresponding author. E-mail addresses: [email protected], [email protected] (K.F. Binmoeller). http://dx.doi.org/10.1016/j.tgie.2017.03.006 0049-0172/& 2017 Elsevier Inc. All rights reserved.

For GV, injection therapy with sclerosants, such as polidocanol or pure alcohol, was abandoned early on because of high recurrent bleeding rates of 37%-89% and a high incidence of complications including gastric ulcerations and perforation [6-8]. Sclerotherapy

F. Weilert, K.F. Binmoeller / Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

has been largely replaced by band ligation for the treatment of EV, and therefore is mostly of historical interest. 3.2. Fibrin glue and thrombin injection Noncyanoacrylate (CYA) sealants, including fibrin glue and thrombin, have been used to arrest variceal bleeding in small uncontrolled case series [9,10]. Thrombin plus ethanolamine was found to be equivalent to ethanolamine alone in 1 randomized controlled trial [11]. In 2 retrospective studies, thrombin reportedly achieved hemostasis in bleeding GV in 75%-94% [12,13]. There have been no reported adverse events, specifically no reports of distant embolization of thrombin. Bovine thrombin (with its putative risk of Creutzfeldt-Jakob disease) has been replaced by human formulation, but still does not negate the potential risk of unknown infections (pooled from 4000-5000 plasma donors). Rebleeding rates of 12%-30%, usually within 3 months, are still of concern [9,12,13], and obliteration of the feeding varix is achieved in only 6% [13]. Current evidence does not support the use of fibrin glue and thrombin injection for the treatment of GV bleeding [14].

91

4. Radiological treatment of GV Radiological intervention is used as a rescue strategy when endoscopic treatment fails, or as a primary intervention when endoscopic expertise is not available. These techniques, however, have limited availability as they are specialized radiological interventions. 4.1. Transjugular intrahepatic portosystemic shunt Decompression of the portal system by placement of a transjugular intrahepatic portosystemic shunt (TIPS) is frequently used for the treatment of portal hypertension and its complications [22]. The effectiveness of TIPS has been well documented in the treatment of acute variceal bleeding [23,24], in the prevention of recurrent variceal bleeding [25], and in the management of refractory ascites [26]. Many patients with GV have a lower portocaval pressure gradient due to extensive spontaneous portosystemic shunts, explaining the reduced efficacy of TIPS in a subset of patients with GV [27].

3.3. Band ligation

4.2. Balloon-occluded retrograde transvenous obliteration

Endoscopic variceal ligation (EVL), widely practiced around the world, is considered appropriate treatment for junctional varices that are an extension of EV. However, EVL may not be appropriate for very large junctional varices that cannot be completely ligated by the band. The results of EVL for nonjunctional GV have not been favorable [6]. Prospective trials have reported high rebleeding and recurrence rates in excess of 50% (54%-72% and 59%-78%, respectively) for the treatment of GOV2 and IGV [1,15,16].

Balloon-occluded retrograde transvenous obliteration (B-RTO) is a method of treating GV that are associated with a gastrorenal shunt. Angiographic balloon occlusion of the gastrorenal shunt is performed to stagnate blood followed by injection of a sclerosant into the GV. Drawbacks include worsening of EV, hepatic and renal toxicity related to a high volume of injected sclerosant, and embolism (pulmonary and cerebral). Combination of B-RTO with endoscopic treatment may improve clinical outcomes. Akahoshi et al [28] compared endoscopic CYA injection with CYA plus B-RTO as a secondary prevention strategy and showed that the addition of B-RTO significantly reduced cumulative rebleeding rates at 5 years and the number of treatment sessions. Balloon-occluded endoscopic injection sclerotherapy (BO-EIS) is a variation of B-RTO where a sclerosant is injected endoscopically after selective angiographic balloon occlusion. A randomized trial comparing BO-EIS to B-RTO showed the 2 techniques to achieve an 89%-90% obliteration of GV, but with a significant reduction in the volume of sclerosant using BO-EIS and with no worsening of EV [29]. Modified percutaneous transhepatic variceal embolization, with or without B-RTO, was found to be superior to endoscopic CYA obliteration with reduced 3-year rebleeding rates (49% vs 84%) [30].

3.4. Detachable loops Owing to the larger diameter of detachable nylon loops compared with bands, loops have been used for the treatment of large ( 42 cm) GV. Lee et al [17] reported an endoscopic hemostasis rate of 82.9% with an early recurrent bleeding rate of only 10.5%. However, they also reported a cumulative recurrence rate of GV of 100%. Retreatment for most of their patients was with an alternative method rather than their preferred initial therapy with detachable loops. Cipoletta et al [18] reported another small series (n ¼ 7) with excellent initial hemostasis and low early rebleeding rates. From a technical perspective, “freehand” loop ligation for varix capture is likely to be challenging owing to the loop slipping off the surface during closure. Our concern is incomplete ligation of the varix that can lead to severe bleeding during deployment and after ischemic sloughing, as reported by Lo and Lai [19].

5. CYA-based treatment of GV

3.5. Hemostatic powders

5.1. CYA monomer types

Topical hemostatic powders, such as Hemospray (Cook Medical Inc, Bloomington, IN), have been used for the management of variceal bleeding. Holster et al [20] reported the use of Hemospray as salvage therapy for persistent bleeding from GOV2 in a patient despite initial CYA injection. Ibrahim et al [21] reported an openlabel case series of 38 patients with acute variceal bleeding (GV in 10% and IGV2 in 6.6%) treated with Hemospray as primary therapy. Clinical hemostasis was claimed in 29 of 30 (96.7%) even though only 13 of 30 (43.4%) had active bleeding at the time of endoscopy. Elective band ligation for EV and CYA for GV was performed at follow-up endoscopy. These authors promoted the use of Hemospray owing to its ease of use, especially in the setting where experienced endoscopists are not immediately available. The use of hemostatic powders for treatment of variceal bleeding is considered investigational at this time.

A variety of CYA glue monomers are commercially available, differing in the length of their alkyl group. N-butyl-2-cyanoacrylate (NB2-CYA) (Histoacryl, B. Braun Medical Inc, Bethlehem, PA), with a 4-carbon alkyl group, has been most widely used for the treatment of GV. The polymerization time of NB2-CYA is rapid and can result in premature solidification of the glue in the needle or entrapment of the needle within the varix. Dilution of NB2-CYA with Lipiodol (ratios ranging from 1:1-1:1.6) is commonly performed to delay the polymerization time. The injection catheter should be primed with sterile water rather than saline, as saline accelerates polymerization. Compared with NB2-CYA, 2-octylcyanoacrylate (2O-CYA) has a longer carbon alkyl group [8] and a longer polymerization time. It can, therefore, be injected without Lipiodol dilution and at a slower rate (1 mL per 30-60 second) [31]. The injection catheter can be primed and flushed with saline

92

F. Weilert, K.F. Binmoeller / Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

because there is no risk of premature solidification within the catheter. 5.2. Endoscopic CYA glue injection Endoscopic therapy of GV with CYA is recommended as firstline therapy by the Baveno VI consensus document [32] and by the American Association for the Study of Liver Diseases guidelines for variceal bleeding [33]. The freehand injection technique under direct endoscopic guidance has been the standard method of glue delivery. When endoscopic ultrasound (EUS) is available, CYA delivery under ultrasound guidance can be performed. 5.2.1. Direct (freehand) endoscopic injection technique In preparation for endoscopic injection of CYA, silicone oil is smeared onto the endoscope tip and flushed through the instrument channel to minimize the risk of glue adherence that can lead to endoscope damage. After puncture of the targeted varix, an initial injection with water or saline should be free flowing into the varix and not form a submucosal injection. Aspiration is not recommended as contact with blood will trigger polymerization and may lead to premature clogging of the injection catheter. Glue is injected into the varix in aliquots of 0.5-1.0 mL. The injection time will vary depending on the type of CYA used and amount of dilution; undiluted NB2-CYA must be rapidly injected over seconds, whereas undiluted 2O-CYA can be injected more slowly over a minute. After the glue has been injected, the glue in the catheter dead space (approximately 1 mL) is flushed out with sterile water or saline to deliver the entire glue content into the varix. Continuous flushing will keep the needle patent for a possible repeat injection. The varix is palpated with a blunt-tipped instrument (eg, closed biopsy forceps) to confirm variceal “hardness” after glue obliteration; if soft, additional injections are performed. 5.2.2. Results of direct endoscopic CYA injection NB2-CYA has been reported in a number of sizable case series with hemostasis rates of greater than 90%, variceal obliteration rates of 70%-90%, and rebleeding rates less than 30% [4,34]. As secondary prophylaxis, CYA injection has been shown to reduce rebleeding rates compared with band ligation [1] and propranolol [35]. As primary prophylaxis, CYA has been shown to reduce the risk of bleeding and mortality from GOV2 or IGV1 greater than 10 mm in size compared with propranolol alone [36]. Rengstorff and Binmoeller [34] reported on the use of 2O-CYA in 25 patients with GV with similar hemostasis rates and a 4% rebleeding rate over 11 months. 5.3. EUS-guided CYA injection Delivery of CYA under EUS guidance has several advantages over direct endoscopic injection, including ensuring precise delivery of glue into the varix lumen. EUS also enables assessment with Doppler to confirm vessel obliteration after treatment. This may have prognostic significance, as rebleeding risk after CYA injection has been linked to residual patency of treated varices [37,38]. Furthermore, treatment can be performed without dependency on direct varix visualization; even in the presence of retained food or blood that may obstruct the endoscopic view, the varix lumen can be accurately targeted for glue injection. EUS can identify the main feeding vein that derives from the left gastric venous trunk, the posterior gastric vein, short gastric vein, or outflowing venous system [38,39] with gastrorenal shunts [40]. Romero-Castro et al [41] described a small case series targeting the perforating “feeder vessel,” rather than the varix lumen proper, under EUS guidance. Targeting the perforating

vessel conceptually may minimize the amount of CYA needed to achieve obliteration of GV, and thereby reduce the risk of embolization. The glue-Lipiodol mixture enabled fluoroscopic visualization of the injected vessel and confirmation that the feeder vessel had been accurately targeted. No rebleeding or complications were observed. The limitation of this approach is that identification of the perforating vessel with EUS can be difficult and time consuming. Importantly, as the perforating vessel may be afferent or efferent, contrast medium must be injected before treatment to determine directional flow relative to the varix. 5.3.1. Transesophageal injection The gastric fundus is well visualized on EUS with the transducer positioned in the distal esophagus. We elected to treat fundal GV from the esophagus with the echoendoscope in an orthograde position. This has several advantages over the conventional positioning of the echoendoscope in (partial) retroflexion within the upper stomach. The transesophageal approach is not hindered by gastric contents, such as blood and food, which tend to accumulate in the fundus. There is also no disruption of the gastric mucosa overlying the varix, which is usually thinned and at high risk of “back-bleeding” after varix puncture. The transesophageal approach allows visualization of the diaphragmatic crus muscle that is typically “sandwiched” between the esophageal and gastric fundic walls. When visualized, we intentionally include the crus muscle in our path of access to fundal GV (“transcrural” puncture), hypothesizing that the crus muscle—a thick fibromuscular bundle approximately 1 cm in thickness—acts as a stabilizing “backboard” to fundal GV. 6. Reducing the risk of CYA embolization The most feared and serious adverse event of CYA glue injection is systemic embolization [42]. Reported events include pulmonary embolism, splenic vein and portal vein thrombosis, splenic infarction, and sepsis secondary to tissue necrosis caused by embolized glue with secondary septic focus [43-51]. Embolization into the arterial circulation (via a patent foramen ovale or arteriovenous pulmonary shunt) can result in stroke and multiorgan infarction [50,51]. Other adverse events include visceral fistulization [52] that may occur after paravariceal injection [35]. Romero-Castro et al [53] demonstrated a high frequency of CYA pulmonary embolization in patients with GV, occurring in 58% of patients treated with NB2-CYA diluted 1:1 with Lipiodol. This was based predominantly on radiological documentation of pulmonary emboli in 9 asymptomatic patients, whereas 2 symptomatic patients presented with chest pain and fever, respectively. Factors that may increase the embolization risk include over dilution of NB2-CYA with Lipiodol, excessively rapid injection, injection of too large volume of glue in a single injection, and IGV1 that have high blood flow rates. To address these concerns, variations of the EUS-guided approach have been investigated. 6.1. EUS-guided coiling Two small case series have described deployment of commercially available stainless steel coils. Levy et al [54] used a 22-gauge needle loaded with a “microcoil.” The stylet was used to advance the constrained coil to the tip of the needle. Once the needle was inserted into the largest varix, the stylet was used to deliver the coil. Two additional coils were placed into separate varices. Romero-Castro et al [55] used a 19-gauge needle to deliver 0.035 in coils of 50-150 mm length (coil diameter of 8-15 mm after deployment). In 1 patient with a large gastrorenal shunt, the investigators failed to achieve obliteration of GV despite

F. Weilert, K.F. Binmoeller / Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

deployment of 13 coils. A further 9 coils were deployed at a subsequent treatment session. The investigators did not comment on cost, but this becomes a consideration when large numbers of coils are required to achieve obliteration. 6.1.1. Comparison of EUS-guided CYA injection vs coiling Romero-Castro et al [53] recently reported on a retrospective 4-year cohort study, comparing EUS-guided CYA injection with EUS-guided coil embolization in 30 patients (23% never bled). Two-thirds had CYA injection, and one-third received coil insertion with an overall obliteration rate of 97%. A higher number of treatment sessions were required to achieve complete obliteration in the CYA vs coil group (P ¼ NS), with a single session achieving complete obliteration in 82% of the coiled group. Adverse events were significantly higher in the CYA (58%) vs the coil (9%) group (P o 0.01). Fujii-Lau et al [56] reported in a small uncontrolled retrospective series that EUS-guided coil with (n ¼ 4) or without (n ¼ 10) concomitant glue injection demonstrating an excellent clinical effect. The small sample size and multiple types of varices targeted did not allow the authors to draw any specific conclusions. 6.2. Combined EUS-guided coiling and CYA injection The deployment of a coil before CYA injection is a hybrid approach that offers several advantages as follows: (1) the coil itself contributes to varix obliteration and hemostasis; (2) the coil’s synthetic fibers bind the glue at the site of coil deployment, which may prevent glue embolization (Figure 1). We reported on our first use of combined coil and CYA injection as “rescue” treatment after standard endoscopy-guided CYA treatment failed in a patient with massive bleeding from fundal GV [57]. This was followed by a series of 30 patients with large fundal

93

GV treated by a standardized coil-glue protocol [58]. The procedure was successful in all patients, with immediate hemostasis achieved in cases of active bleeding. The average volume of 2OCYA injected was 1.4 mL per patient after coil deployment. Of note, this was 1 mL less than the average amount injected per patient in our previous study using the same CYA injected alone [34]. Of 24 patients who underwent follow-up endoscopy, 23 (96%) had complete variceal obliteration after a single treatment session, with no intravariceal flow on EUS color Doppler imaging. Recurrent bleeding developed in 1 patient at 21 days. This patient underwent a second successful treatment with EUS-guided coil and CYA. No patient required surgical or percutaneous shunt procedures. 6.2.1. Long-term outcomes We recently reported on long-term outcomes of 152 patients who received EUS-guided combined coiling and 2O-CYA therapy for fundal varices over a 6-year period [59]. Technical success was achieved in 151 of 152 patients, while procedure-related adverse events occurred in 7% of patients, including self-limited abdominal pain (n ¼ 4), delayed self-limited bleeding from coil or glue extrusion at the injection site (n ¼ 4), and delayed (1 week) pulmonary embolism (n ¼ 1). Of note, the patient who developed pulmonary embolism was asymptomatic after treatment and had been discharged from the hospital. Management of pulmonary embolism was conservative with an uneventful course. Mean follow-up in this study was 436 days (range: 30-2043) in 125 patients. A total of 100 patients underwent follow-up EUS examinations, and fundal varices were confirmed to be obliterated in 93 of 100 patients (93%). Importantly, once obliteration was achieved, only 3 of 93 patients (3%) experienced posttreatment bleeding from GV during a mean follow-up of 529 days (range: 30-2043). Overall, recurrent bleeding occurred in 16% (n ¼ 20) with 12

Fig. 1. (A) Large isolated gastric fundal varices in a patient with a history of bleeding. (B) EUS-guided deployment of coil through a 19-gauge FNA needle. (C) One-month follow-up endoscopy showing glue extrusion from eradicated varices. (D) Nine-month follow-up showing eradicated varices. FNA, fine needle aspiration.

94

F. Weilert, K.F. Binmoeller / Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

EGD for known GFV without bleeding (primary prophylaxis)

IGV1 & GOV2

GOV1

Linear EUS and doppler

Assess size / location / feeder vessels. Also assess portal vein and splenic vein patency

Possible EBL

8. Conclusion

Dominant varix of at least 20mm

Dominant varix less than 20mm

Coil and CYA

Surveillance (consider nonselective beta blocker)

The treatment of gastric fundal varices differs fundamentally from EV. Endoscopic injection of GV with CYA is recommended as primary treatment by Baveno VI guidelines. However, EUS-guided therapy has several conceptual advantages, allowing controlled intravascular delivery of vascular coils or CYA or both to achieve high obliteration rates, which achieves low long-term rebleeding rates. Both primary and secondary prophylaxis should be considered as part of standard treatment algorithms.

References

Occluded flow by doppler

Obliteration

retreated. EUS examinations were performed in 28 of 36 patients with follow-up data available, 27 of whom achieved complete obliteration of the primary variceal complex. The remaining patient was found to have residual varices on routine follow-up and was retreated with one 10 mm coil and 1 mL of glue. The high obliteration rate (96%) and acceptable risk profile support consideration for this type of therapy as primary prophylaxis in this group of patients. We propose an algorithm in the approach to primary prophylaxis (Figure 2).

No obliteration

Bleeding

Coil and CYA or CYA alone Occluded flow by doppler

Surveillance

Obliteration

Fig. 2. Proposed algorithmic approach to primary prophylaxis of gastric varices.

patients presenting less than 6 months and 8 patients more than 6 months. The cause of recurrent bleeding was attributed to GV in only 8% (n ¼ 10).

7. Primary prophylaxis Primary prophylaxis of GV remains controversial but deserves consideration. IGV have the highest flow rates, are larger in size, and have deeper feeding vessels, resulting in more severe bleeding episodes [60]. The mortality from the first variceal bleeding event has remained high at 20% within 6 weeks of the index event [3]. When used for primary prophylaxis, CYA injection has been shown to reduce the risk of bleeding and mortality from GOV2 or IGV1 more than 10 mm in diameter compared with propranolol alone [31]. A previous small cohort of patients undergoing primary prophylaxis also showed effectiveness of undiluted CYA and methacryloxysulfolane injection in achieving obliteration of GV [61]. We treated 40 patients with high-risk fundal GV who had never bled with EUS-guided combined coil and glue [59]. In the 37 patients with clinical or EUS follow-up data available (mean follow-up ¼ 449 days; range: 30-2043), only 2 patients experienced minor bleeding (melena with mild drop in hemoglobin and no transfusion needed) more than 1 year after glue and coil treatment (62 and 278 weeks, respectively). Both patients were found to have new varices adjacent to the prior-treated varices and

[1] Tan P, Hou M, Lin H, Liu T, Lee F, Chang F, et al. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl2-cyanoacrylate injection versus band ligation. Hepatology 2006;43:690–7. [2] Caldwell S. Gastric varices: is there a role for endoscopic cyanoacrylate, or are we entering the BRTO era? Am J Gastroenterol 2012;107:1784–90. [3] D’Amico G, de Franchis R. End-of-the-century reappraisal of 6-week outcome of upper gastrointestinal bleeding in cirrhosis. A prospective study. Gastroenterology 1999;117:A1199. [4] Petersen B, Barkun A, Carpenter S, Chotiprasidhi P, Chuttani R, Silverman W, et al. Tissue adhesives and fibrin glue. Gastrointest Endosc 2004;60:327–33. [5] Sarin S, Kumar A. Gastric varices: profile, classification, and management. Am J Gastrenterol 1989;84:1244–9. [6] Trudeau W, Prindiville T. Endoscopic injection sclerosis in bleeding gastric varices. Gastrointest Endosc 1986;32:264–8. [7] Sarin S. Long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience. Gastrointest Endosc 1997;46:8–14. [8] Sarin S, Lahoti D, Saxena S. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992;16:1343–9. [9] Datta D, Vlavianos P, Alisa A, Westaby D. Use of fibrin glue (beriplast) in the management of bleeding gastric varices. Endoscopy 2003;35:675–8. [10] Heneghan M, Byrne A, Harrison P. An open pilot study of the effects of a human fibrin glue for endoscopic treatment of patients with acute bleeding from gastric varices. Gastrointest Endosc 2002;56:422–6. [11] Kitano S, Hashizume M, Yamaga H, Wada H, Iso Y, Iwanaga T, et al. Human thrombin plus 5 percent ethanolamine oleate injected to sclerose oesophageal varices: a prospective randomized trial. Br J Surg 1989;76:715–8. [12] Przemioslo R, McNair A, Williams R. Thrombin is effective in arresting bleeding from gastric variceal hemorrhage. Dig Dis Sci 1999;44:778–81. [13] Yang W, Tripathi D, Therapondos G, Todd A, Hayes P. Endoscopic use of human thrombin in bleeding gastric varices. Am J Gastroenterol 2002 1381–5. [14] Wong Kee Song LM, Banerjee S, Barth BA, Bhat Y, Desilets D, et al, ASGE Technology Committee. Emerging technologies for endoscopic hemostasis. Gastrointest Endosc 2012;75:933–7. [15] Lo G, Lai K, Cheng J. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology 2001;33:1060–4. [16] Tantau M, Crisan D, Popa D, Vesa S, Tantau A. Band ligation vs. N-Butyl2-cyanoacrylate injection in acute gastric variceal bleeding: a prospective follow-up study. Ann Hepatol 2013;13:75–83. [17] Lee MS, Cho JY, Cheon YK, Ryu CB, Moon JH, Cho YD, et al. Use of detachable snares and elastic bands for endoscopic control of bleeding from large gastric varices. Gastrointest Endosc 2002;56:83–8. [18] Cipolletta L, Bianco MA, Rotondano G, Piscopo R, Prisco A, Garofano ML. Emergency endoscopic ligation of actively bleeding gastric varices with a detachable snare. Gastrointest Endosc 1998;47:400–3. [19] Lo GH, Lai KH. Is endoscopic ligation therapy with large detachable snares and elastic bands really safe and effective? Gastrointest Endosc 2003;57:438–9 [author reply 9-40]. [20] Holster IL, Poley JW, Kuipers EJ, Tjwa ET. Controlling gastric variceal bleeding with endoscopically applied hemostatic powder (Hemospray). J Hepatol 2012; 57:1397–8.

F. Weilert, K.F. Binmoeller / Techniques in Gastrointestinal Endoscopy 19 (2017) 90–95

[21] Ibrahim M, El-Mikkawy A, Abdalla H, Mostafa I, Deviere J. Management of acute variceal bleeding using hemostatic powder. United European Gastroenterol J 2015;3:277–83. [22] Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol 2007;41: S344–51. [23] Boyer T, Haskal Z, AASLD practice guideline. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41:1–15. [24] de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2005;43:167–76. [25] D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a metaanalytic view. Hepatology 1995;22:332–53. [26] Gines P, Uriz J, Calahorra B. Transjugular intrahepatic portosystemic shunt versus repeated paracentesis plus intravenous albumin for refractory ascites in cirrhosis. A multicenter randomized comparative study. Gastroenterology 2002;123:1839–47. [27] Fujii-Lau LL, Law R, Wong Kee Song LM, Gostout CJ, Kamath PS, Levy MJ. Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices. Surg Endosc 2016;30(4):1396–404. [28] Akahoshi T, Tomikawa M, Kamori M, Tsutsumi N, Nagao Y, Hashizume M, et al. Impact of balloon-occluded retrograde transvenous obliteration on the management of isolated fundal gastric variceal bleeding. Hepatol Res 2012;424: 385–93. [29] Shiba M, Higuchi K, Nakamura K, Itani A, Kuga T, Okazaki H, et al. Efficacy and safety of balloon-occluded endoscopic injection sclerotherapy as a prophylactic treatment for high risk gastric fundal varices: a prospective, randomized, comparitive trial. Gastrointest Endosc 2002;56:522–8. [30] Wang J, Tian X-G, Li Y, Zhang C-Q, Liu F-L, Cui Y, et al. Comparison of modified percutaneous transhepatic variceal embolization and endoscopic cyanoacrylate injection for gastric variceal bleeding. World J Gastroenterol 2013;19: 706–14. [31] Mishra S, Sharma B, Kumar A, Sarin S. Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta-blockers: a randomized controlled trial. J Hepatol 2011;54:1161–7. [32] de Franchis R, Baveno VIF. Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015;63:743–52. [33] Garcia-Tsao G, Sanyal A, Grace N, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:922–38. [34] Rengstorff D, Binmoeller K. A pilot study of 2-octyl cyanoacrylate injection for treatment of gastric fundal varices in humans. Gastrointest Endosc 2004;59: 553–8. [35] Binmoeller K. Glue for gastric varices: some sticky issues. Gastrointest Endosc 2000;52:298–301. [36] Mishra S, Chander Sharma B, Kumar A, Sarin S. Endoscopic cyanoacrylate injection versus beta-blocker for secondary prophylaxis of gastric variceal bleed: a randomised controlled trial. GUT 2010;59:729–35. [37] Lee Y, Chan F, Ng E, Leung V, Law K, Yung M, et al. EUS-guided injection of cyanoacrylate for bleeding gastric varices. Gastrointest Endosc 2000;52: 168–74. [38] Iwase H, Suga S, Morise K. Color Doppler endoscopic ultrasonography for the evaluation of gastric varices and endoscopic obliteration with cyanoacrylate glue. Gastrointest Endosc 1995;41:150–4. [39] Hino S, Kakutani H, Ikeda H. Hemodynamic analysis of esophageal varices using color Doppler endoscopic ultrasonography to predict recurrence after endoscopic treatment. Endoscopy 2001;33:869–72. [40] Kakutani H, Hino S, Ikeda K. Use of the curved linear-array echo endoscope to identify gastrorenal shunts in patients with gastric fundal varices. Endoscopy 2004;36:710–4. [41] Romero-Castro R, Pellicer-Bautista F, Jimenez-Saenz M. EUS-guided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases. Gastrointest Endosc 2007;66:402–7.

95

[42] Seewald S, Leong T, Imazu H, Naga M, Omar S, Groth S, et al. A standardized injection technique and regimen ensures success and safety of N-butyl2-cyanoacrylate injection for the treatment of gastric fundal varices. Gastrointest Endosc 2008;68:447–54. [43] Berry P, Cross T, Orr D. Clinical challenges and images in GI. Pulmonary embolization of Histoacryl “glue” causing hypoxia and cardiovascular instability. Gastroenterology 2007;133:1413. [44] Chang C, Shiau Y, Chen T, Hou M, Sun C, Liao W, et al. Pyogenic portal vein thrombosis as a reservoir of persistent septicaemia after cyanoacrylate injection for bleeding gastric varices. Digestion 2008;78:139–43. [45] Saracco G, Giordanino C, Roberto N, Ezio D, Luca T, Caronna S, et al. Fatal multiple systemic embolisms after injection of cyaonoacrylate in bleeding gastric varices of a patient who was noncirrhotic but with idiopathic portal hypertension. Gastrointest Endosc 2007;65:345–7. [46] Shim C, Cho Y, Kim J, Bong H, Kim Y, Lee J, et al. A case of portal and splenic vein thrombosis after histoacryl injection therapy in gastric varices. Endoscopy 1996;28:461. [47] Liu C, Tsai F, Liang P, Lee C, Yang P. Splenic vein thrombosis and Klebsiella pneumoniae septicaemia after endoscopic gastric variceal obturation therapy with N-butyl-2-cyanoacrylate. Gastrointest Endosc 2006;63:336–8. [48] Wright G, Matuli W, Zambreanu L, O’Neill S, Smith R, O’Beirne J, et al. Recurrent bacteremia due to retained embolized glue following variceal obliteration. Endoscopy 2009;41(Suppl. 2):E56–7. [49] Cheng P, Sheu B, Chen C, Chang T, Lin X. Splenic infarction after histoacryl injection for bleeding gastric varices. Gastrointest Endosc 1998; 48:426–7. [50] Tan Y, Goh K, Kamarulzaman A, Tan P, Ranjeev P, Salem O, et al. Multiple systemic embolisms with septicamia after gastric variceal obliteration with cyanoacrylate. Gastrointest Endosc 2002;55:276–8. [51] Abdullah A, Sachithanandan S, Tan O, Chan Y, Khoo D, Mohamed Sawawi F. Cerebral embolism following N-butyl-2-cyanoacrylate injection for oesophageal postbanding ulcer bleed: a case report. Hepatol Int 2009;3: 504–8. [52] Battaglia G, Morbin T, Patarnello E, Merkel C, Corona MC, Ancona E. Visceral fistula as a complication of endoscopic treatment of esophageal and gastric varices using isobutyl-2-cyanoacrylate: report of two cases. Gastrointest Endosc 2000;52:267–70. [53] Romero-Castro R, Ellrichmann M, Ortiz-Moyano C, Subtil-Inigo J, JunqueraFlorez F, Gornals J, et al. EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study. Gastrointest Endosc 2013;78:711–21. [54] Levy M, Wong Kee Song L, Kendrick M. EUS-guided coil embolization for refractory ectopic variceal bleeding. Gastrointest Endosc 2008;67:572. [55] Romero-Castro R, Pellicer-Bautista F, Giovannini M. Endoscopic ultrasound (EUS)-guided coil embolization therapy in gastric varices. Endoscopy 2010; 42(Suppl. 2):E35–6. [56] Fujii-Lau LL, Law R, Wong Kee Song LM, Gostout CJ, Kamath PS, Levy MJ. Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices. Surg Endosc 2015. [57] Sanchez-Yague A, Shah J, Nguyen-Tang T. EUS-guided coil embolization of gastric varices after unsuccessful endoscopic glue injection. Gastrointest Endosc 2009;69:AB6. [58] Binmoeller K, Weilert F, Shah J, Kim J. EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection. Gastrointest Endosc 2011;74:1019–25. [59] Bhat YM, Weilert F, Fredrick RT, Kane SD, Shah JN, Hamerski CM, et al. EUSguided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years (with video). Gastrointest Endosc 2016;83:1164–72. [60] de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001;5:645–63. [61] Franco MC, Gomes GF, Nakao FS, de Paulo GA, Ferrari AP Jr, Libera ED Jr. Efficacy and safety of endoscopic prophylactic treatment with undiluted cyanoacrylate for gastric varices. World J Gastrointest Endosc 2014;6: 254–9.