J Hepatobiliary Pancreat Sci (2015) 22:44–50 DOI: 10.1002/jhbp.183
TOPIC
Endoscopic ultrasound-guided intravascular therapy Kenneth F. Binmoeller · Oriol Sendino · Steven D. Kane
Published online: 4 November 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional endoscopic ultrasound (EUS) has enabled access to these structures with a standard fine-needle aspiration (FNA) needle. Sclerosants, cyanoacrylate, and coils can be delivered through the lumen of the FNA needle. EUS-guided treatment of gastric varices has theoretical advantages over conventional endoscopy-guided treatment. Controlled studies are needed to determine the role of EUS-guided treatment for primary and secondary prevention of variceal bleeding. There is a growing list of novel indications for EUS-guided vascular therapy that include portal vein angiography and pressure measurements, intrahepatic portosystemic shunt placement, and micro coil embolization of vascular structures. Additionally, access and therapy of the heart and surrounding structures appears feasible. Keywords Endoscopic ultrasound · Gastrointestinal bleeding · Vascular access Introduction Vessels have been a target for therapy by interventional radiology for several decades now. Refractory gastrointestinal (GI) bleeding is treated by selective angiographic embolization. Transjugular intrahepatic portosystemic shunt (TIPS) is widely used for refractory bleeding esophageal or gastric varices (GV) associated with portal hypertension [1, 2]. Placement of endovascular grafts is now mainstream and the first reports of trans-aortic valve implantation (TAVI) have emerged [3]. K. F. Binmoeller (*) · O. Sendino · S. D. Kane Paul May and Frank Stein Interventional Endoscopy Services, California Pacific Medical Center, Suite 600, Stanford Building, 2351 Clay Street, San Francisco, CA 94115, USA e-mail: [email protected]
Endoscopic ultrasound (EUS) offers an attractive alternative approach to interventional radiological vascular therapy of vessels in close proximity to the GI tract. Major vascular structures including the heart, aorta, celiac axis, portal vein (PV), hepatic veins, mesenteric vessels, and aberrant vascular shunts such as speno-renal shunts associated with portal hypertension are easily identified. Even smaller vascular structures such as the gastro-duodenal artery, splenic vessels, hepatic artery, and PV branches can be confidently traced and identified.
Non-variceal gastrointestinal bleeding Endoscopic techniques for the treatment of non-variceal GI bleeding include the injection of epinephrine [4–6], thermal contact therapy [7–10], mechanical hemostasis with clips [11], and band ligation [12]. These modalities are well established and effective in the majority of cases, but may fail in up to 15% of cases [13]. EUS-guided vascular therapy was first reported in a case series of five patients, four with refractory bleeding from hemosuccus pancreaticus, a Dieulafoy’s lesion, duodenal ulceration, and a GI stromal tumor (GIST) [14]. These patients had presented with an average of three prior bleeding episodes, required multiple units of packed red blood cells, and repeated endoscopic and vascular therapies, all of which were ineffective. EUS-guided injection therapy of absolute alcohol and/or cyanoacrylate (CYA) was delivered directly into the bleeding vessels. Real-time monitoring by Doppler ultrasound was used to conclude the injection therapy when no visible flow could be seen in the bleeding vessel. Control of the bleeding source was achieved in all of these refractory cases without any complications. We have successfully injected CYA glue into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. The technique is shown in Figure 1, Video S1.
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Fig. 1 Cyanoacrylate glue injection into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. (a) Doppler showing feeder vessel traversing the gastric wall; (b) Glue injection through the fine-needle aspiration needle in feeder vessel
Esophageal variceal bleeding Endoscopic band ligation is well established as the preferred technique for primary and secondary therapy of esophageal varices [15–17]. Injection of sclerosants [18] has been used as rescue therapy when band ligation fails to eradicate varices. Rebleeding after endoscopic therapy is thought to be secondary to failure to treat perforating veins and collateral vessels that feed esophageal varices [19, 20]. EUS enables the visualization of perforating veins and collaterals for targeted sclerotherapy [20–22]. Lahoti et al. [23] first reported the use of EUS-ES to achieve variceal obliteration in 2000. The injection of sclerosant was directed at the perforating vessels until flow was no longer seen. All five treated patients achieved variceal obliteration after an average of 2.2 sessions. No recurrent bleeding was reported after a mean follow-up period of 15 months. De Paulo et al. [24] reported a randomized controlled trial of 50 patients comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins. They found similar rebleeding rates after similar numbers of sessions to achieve obliteration, but rebleeding was found to be significantly associated with the presence of collateral vessels. Currently EUS-guided sclerotherapy of esophageal varices should be reserved for patients with bleeding refractory to band ligation and conventional sclerotherapy.
Gastric variceal bleeding GV are less common than esophageal varices, but may be present in up to 20% of patients with portal hypertension. As many as 65% of GV will bleed over 2 years [25]. The results of variceal ligation for GV have been poor, which is not surprising given the larger size of GV [26]. Direct endoscopic CYA injection of GV, first described by Soehendra and colleagues in the 1980s, is widely considered first-line therapy [27]. N-butyl-2-cyanoacrylate has been used in multiple case series and randomized trials with hemostasis rates
of 58% to 100% and rebleeding rates of 0% to 40% [15]. Our group reported on the use of 2-octyl-cyanoacrylate in 25 patients with GV with similar hemostasis rates and a 4% rebleeding rate over 11 months [28]. The role of EUS in the management of GV is foremost diagnostic. Owing to the location in the deep submucosal layer of the stomach, GV may be difficult to detect or differentiate from prominent gastric folds on endoscopy. Boustiere et al. [29] found that the use of EUS increases the detection of fundal varices six-fold. Even when detected, the visualized portion may be only the tip of the iceberg. Lee et al. [30] demonstrated that performing EUS to monitor GV obliteration after glue injection and performing repeated CYA injections when incompletely obliterated reduced the risk of bleeding with a possible reduction in mortality when compared with “on-demand” injections alone. Similarly, Iwase et al. [31] showed residual patency of treated varices correlated with rebleeding risk after glue injection. Varix obliteration can be confirmed by the absence of blood flow on color Doppler. EUS has conceptual advantages to guide the injection of glue into GV. Endoscopy-guided injection has the limitation that targeting is “blind” and may result in injection adjacent to the varix (paravariceal), missing the varix lumen. Data from sclerotherapy suggests that up to 60% of injections are actually paravariceal [26]. EUS-guided glue injection is attractive as it enables sonographic visualization of glue delivery into the varix lumen. Furthermore, it allows for visualization of deeper varices as well as the feeding vein system, which derives from the left gastric vein trunk, the posterior gastric vein, short gastric vein or outflowing vein system [31, 32] with gastro-renal shunts [33]. Another advantage of EUS-guided treatment is the lack of dependency on direct varix visualization when performing treatment. 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. Romero-Castro et al. [34] described a small case series targeting the “feeder vessel,” rather than the varix lumen proper, under EUS-guidance. The rationale for targeting the
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feeder vessel was to minimize the amount of CYA needed to achieve obliteration of GV and thereby reduce the risk of embolization. The authors targeted the feeder vein using a 1:1 mixture of N-butyl-2-cyanoacrylate and lipiodol. The lipiodol enabled fluoroscopic visualization of the injected vessel and confirmation that it had been accurately targeted. There was no rebleeding or complications observed. It should be noted that the identification of the feeder vessel with EUS can at times be difficult, as was acknowledged by the authors. Further, because the perforating vessel may be afferent or efferent, contrast should be injected prior to treatment to determine directional flow relative to the varix.
EUS-guided coiling A major, potentially life-threatening risk of glue injection of GV is systemic embolization, primarily via highly prevalent splenorenal and gastrorenal portosystemic shunts [35]. Inflammatory reactions to CYA include pain and fever, and local tissue inflammation can result in ulceration [36]. Entrapment of the needle in the varix by glue and damage to scope has also been reported [37, 38]. To avoid complications related to the use of glue, case series have described the deployment of commercially available stainless steel coils to obliterate varices. Most coils used in interventional radiology fit through EUS-fine-needle aspiration (FNA) needles and can be used for EUS-guided therapy. The coils used at our institution are made of Inconel, a nickel-based superalloy. The coil contains radially extending, synthetic fibers that help induce clot and hemostasis. The coils are magnetic resonance imaging (MRI) conditional and can be used in a static magnetic field of 3 Tesla or less. A variety of sizes and lengths are available. A 0.035-inch coil will fit through a 19-gauge FNA needle. Extended length ranges from 2 to 15 cm, with coiled diameter ranging from 2 to 20 mm and approximate number of loops from 1.9 to 5.6. Smaller 0.018-inch coils are also available and will fit through a 22-gauge FNA needle. Coil selection should depend on the size of the varix, but typically a coiled diameter of 10–20 mm is used. In 2008, Levy et al. [39] reported the first case of EUSguided coil injection for acute ectopic gastric variceal bleeding. They advanced a total of three embolization microcoils through a 22-gauge EUS-FNA needle for variceal obliteration. The length of the coil was loaded into the needle hub and advanced to the tip of the needle using a stylet. The varix was punctured with the FNA needle and the stylet was further advanced to deliver the coil. Rebleeding occurred, but was successfully treated with two additional coils placed into untreated varices. Romero-Castro [40] used coils of 0.035-inch diameter, 50–150 mm length, and diameter of
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8–15 mm, deployed through a 19-gauge needle. In one patient with a large gastro-renal shunt the authors failed to achieve obliteration of GV despite deployment of 13 coils. The authors subsequently delivered nine additional coils into the perforating feeding vein. Cost becomes an obvious consideration when using such large numbers of coils to achieve varix obliteration. A recent retrospective trial of 30 patients comparing EUS-guided coil injection to EUS-guided CYA injection revealed similar obliteration rates, but fewer endoscopy sessions were required in the coil group (82% obliteration in a single session compared to 53%) [41]. Of note, the intended therapy was for coil injection in all, but technical difficulties hindering the use of coils were encountered in 19 of 30 patients, resulting in only 11 treated with coils. The rates of adverse events were significantly higher in the CYA vs. the coil group (58% vs. 9%), although nine of the 11 adverse events in the CYA group were asymptomatic pulmonary glue embolisms found on routine postprocedure CT. This conclusion was that glue embolization is likely more common than appreciated, but that it rarely causes symptoms.
EUS-guided cyanoacrylate injection and coiling (Fig. 2, Video S2) Our center has developed an EUS-guided approach consisting of coil placement, immediately followed by glue injection into the same varix. We theorized that the coil provides a scaffold for glue retention at the site of intravariceal injection. Our ex-vivo work has shown that glue immediately adheres to the fibers of a “wool coil” when immersed in a container of heparinized blood [42]. The combination of coil and glue may increase hemostasis and varix obliteration rates while decreasing the risk of embolization. The clinical protocol at our center for combined EUSguided coil and glue is as follows: (1) Standard upper endoscopy to establish candidacy for glue and coil treatment. (2) Prophylactic antibiotics are given. (3) EUS with a curvilinear array echoendoscope and intraluminal water filling of the gastric fundus for improved sonographic visualization. (4) EUS-guided coil placement: The varix is punctured from the distal esophagus or cardia with a 19- or 22-gauge, salineprimed, FNA needle (needle size based on size of coil to be delivered). After puncture, intravariceal needle position is confirmed by blood aspiration or saline injection (bubbles visualized endosonographically). The coil is delivered into the varix by using the needle stylet as a pusher, and can be sonographically visualized as a curved echogenicity. Care is taken to ensure that advancement of the coil does not force the needle back out of the varix lumen. (5) After the coil is deployed, blood is again aspirated to ensure the needle
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Fig. 2 Endoscopic ultrasound (EUS)-guided coil and glue therapy for gastric fundal varices. (a) Fundal varix, with EUS image (insert); (b) deployment of coil (arrow) through the 19-gauge needle; (c) glue and coil complex (arrow) after injection of cyanoacrylate glue through the 19-gauge needle; (d) eradication of fundal varices on 9 months follow-up endoscopy
remains in the lumen of the varix. Undiluted 2-octylcyanoacrylate (1 ml) is immediately injected over 30–45 s, followed by normal saline to flush the glue through the dead space of the catheter. (6) After glue injection, the varix is interrogated with EUS and color Doppler is used to confirm absence of flow. Additionally, switching to a diagnostic gastroscope, the varix can be endoscopically probed in retroflexion with a closed forceps to assess induration. Further injections of aliquots of 1 ml of glue or repeat combination of coil and glue are used as needed for complete obliteration of all varices. If concomitant esophageal varices are seen, conventional band ligation is performed after glue/ coil treatment. We reported our first use of coil and CYA as “rescue” treatment after standard endoscopy-guided CYA treatment failed in a patient with massive gastric fundal variceal (GFV) bleeding [43]. We later reported our experience using a combined approach of CYA injection after deployment of a single coil in a series of 30 patients with GFV. The coil diameter after deployment (up to 20 mm) was selected to approximate that of the lumen of the targeted varix. Combined coil and glue therapy was found to be safe and effective in eradicating gastric fundal varices with only a single treatment session required in 96% of the patients [44]. Immediate hemostasis was achieved in all patients with active bleeding. Rebleeding from incompletely treated GV occurred in one patient; apart from this, there were no adverse events. No patients required surgical or percutaneous shunt procedures. The average volume of CYA (2-octyl-cyanoacrylate) 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 [38]. There was no damage to the echoendoscope related to glue injections and no procedurerelated complications. We have applied the technique of glue and coil injection for the treatment of large bleeding rectal varices [45]. The gastric fundus can be well visualized on EUS with the transducer positioned in the distal esophagus or at the cardia. Since the echoendoscope does not enter into the support, EUS-guided access to GFV 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. We have used both a conventional and a prototype forward view (FV) curved linear array (CLA) echoendoscopes for EUS-guided treatment. We found the FV-CLA instrument to have several technical advantages: (1) more perpendicular needle orientation to the target lesion; (2) uniaxis instrumentation imparting an increased forward transfer of force to the tip of the needle; (3) frontview optics that improve endoscopic visualization; and (4) accessory water jet channel for water filling and irrigation. These advantages have been previously described in other clinical applications of the FV-CLA echoendoscope [44, 46]. Comparative studies are needed to determine the benefit of combined CYA and coil treatment of GV over CYA alone, as well as the advantages of EUS-guidance over endoscopy-guidance.
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Fig. 3 (a) Endoscopic ultrasound view showing placement of dual-flanged metal stent– intrahepatic porto-systemic shunt across inferior vena cava (IVC) and portal vein (PV); (b) Necropsy specimen confirming lumen apposing stent positioning across IVC and PV
Portal vein angiography and pressure measurements PV angiography and pressure measurements can add important clinical information for the management of patients with chronic liver disease and portal hypertension. Direct transcutaneous transhepatic portal pressure measurements are hampered by technical difficulties and a high rate of complications [45]. EUS may permit PV access, contrast injection and monitoring the PV pressure [47]. Direct measurements of the PV pressure under EUS guidance was first reported by Lai et al. [48] in the animal model. A 22-gauge FNA needle was advanced under EUS guidance into the extrahepatic PV and pressure measurements were obtained. Giday performed EUS-guided transhepatic PV catheterization with a modified ERCP catheter, which allowed them to perform portal angiography and obtain continuous portal pressure readings over one hour. Results showed minimal variability within each animal. The position of the catheter inside the PV was stable and was not influenced by the animal’s respiratory or endoscope movement [49]. A transhepatic route for catheter placement into the PV was selected based on the theory that hepatic parenchyma surrounding the catheter will tamponade the track after catheter removal and thereby prevent postprocedural bleeding [49].
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 [1]. The effectiveness of TIPS has been well documented in the treatment of acute variceal bleeding [2, 27], the prevention of recurrent variceal bleeding [50] and the management of refractory ascites [51]. TIPS is
a widely used technique, predominantly performed by interventional radiologists, and limited to tertiary-referral centers. Buscaglia first described EUS-guided creation of an intrahepatic portosystemic shunt (IPS) in a live porcine model [52]. Under direct EUS observation, the HV and the PV were sequentially punctured with a 19-gauge FNA needle following which a guidewire was advanced through the needle into the PV. A self-expandable tubular metal stent was inserted over the guidewire and deployed with its distal end inside the PV and the proximal end inside the HV. All steps of the procedure were clearly seen by EUS. Our group [53] recently reported on the use of a lumenapposing stent in the endoscopic creation of a transgastric IPS. The AXIOS (Xlumena, Mountain View, CA, USA) is a fully coated, dual-flanged metal stent constrained in a 10.5 Fr delivery catheter. When expanded, the flange and body diameters measure 10 mm and 4 mm, respectively. The length of the AXIOS is 8 mm. A therapeutic 3.7 mm working channel echoendoscope was advanced into the stomach of five healthy animals and used to locate the PV and inferior vena cava (IVC). A 0.035 guidewire was advanced and placed into the PV. The needle was then exchanged for the AXIOS delivery catheter. The distal anchor flange of the AXIOS was deployed in the PV and the proximal anchor flange was deployed in the IVC (Fig. 3). Gross necropsy on all animals confirmed stent placement between the PV and IVC and no evidence of tissue injury or hematoma.
Microcoil embolization Interventional radiologists have performed selective embolization of the right branch of the PV to produce compensatory hypertrophy of the left hepatic lobe in patients
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undergoing right hepatectomy. Preliminary results in an animal model [54] suggest EUS-guided coil embolization of the right PV can produce the intended hypertrophy of the left hepatic lobe. Matthes et al. [55] reported on the injection of the polymer (Enteryx) into the main PV, to occlude the vessel. These anecdotal reports in the animal model support a role for EUS-guided delivery of different devices or compounds to occlude small and large vessels. Further studies are needed to determine the potential benefit over percutaneous approaches. Access to the heart The proximity of the heart to the esophagus lends itself to EUS-guided intervention. Fritscher-Ravens et al. [56] described EUS-guided puncture of the heart. In porcine studies, an FNA needle could be introduced repeatedly into the left atrium, followed by the injection of saline. Reaching the aortic valve was thought to be more difficult because of the moving target, but ablation therapy was felt to be technically possible. The coronary artery was successfully punctured in several of the animals. No significant injury was observed in two acute and six survival animals. The authors also reported EUS-guided pericardial fluid aspiration in three patients and puncture of a left atrial mass in a third patient. Conclusion The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional EUS has enabled access to these structures with a standard FNA needle. Sclerosants, CYA and, more recently, coils can be delivered through the lumen of the FNA needle. Data are still very limited and multicenter, prospective controlled trials are needed to show clinical effectiveness and safety in humans. The development of new tools designed for EUS-guided vascular therapy is needed. Conflict of interest
None declared.
References 1. Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol. 2007;41:S344–51. 2. Boyer T, Haskal Z. AASLD practice guideline. The role of transjugular intra-hepatic portosystemic shunt in the management of portal hyper- tension. Hepatology. 2005;41:1–15. 3. Webb J, Cribier A. Percutaneous transarterial aortic valve implantation. Eur Heart J. 2011;32:140–7.
49 4. Lin H, Hsieh Y, Tseng G. A prospective, randomized trial of largeversus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc. 2002;55:615–19. 5. Song S, Chung J, Moon YM. Comparison of the hemostatic effect of endoscopic injection with fibrin glue and hypertonic salineepinephrine for peptic ulcer bleeding: a prospective randomized trial. Endoscopy. 1997;29:827–33. 6. Kubba A, Murphy W, Palmer KR. Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin. Gastroenterology. 1996;111:623–8. 7. Kanai M, Hamada A, Endo Y. Efficacy of argon plasma coagulation in nonvariceal upper gastrointestinal bleeding. Endoscopy. 2004;36:1085–8. 8. Chau C, Siu W, Law B. Randomized controlled trial comparing epinephrine injection plus heat probe coagulation versus epinephrine injection plus argon plasma coagulation for bleeding peptic ulcers. Gastointest Endosc. 2003;57:455–61. 9. Jensen D, Kovacs T, Jutabha R. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology. 2002;123:407– 13. 10. Laine L, Estrada R. Randomized trial of normal saline solution injection versus bipolar electrocoagulation for treatment of patients with high- risk bleeding ulcers: is local tamponade enough? Gastointest Endosc. 2002;55:6–10. 11. Chou Y, Hsu P, Lai K. A prospective, randomized trial of endoscopic hemoclip placement and distilled water injection for treatment of high-risk bleeding ulcers. Gastointest Endosc. 2003;57:324–8. 12. Mumtaz R, Shaukat M, Ramirez F. Outcomes of endoscopic treatment of gastroduodenal Dieulafoy’s lesion with rubber band ligation and thermal/injection therapy. J Clin Gastroenterol. 2003;36:310–14. 13. Longstreth G. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am J Gastrenterol. 1997;92:419–24. 14. Levy M, Wong Kee Song L, Farnell M. Endoscopic ultrasound (EUS)-guided angiotherapy of refractory gastrointestinal bleeding. Am J Gastrenterol. 2008;103:352–9. 15. De Franchis R, Primignani M. Endoscopic treatments for portal hyper- tension. Semin Liver Dis. 1999;19:439–55. 16. Helmy A, Hayes P. Review article: current endoscopic therapeutic options in the management of variceal bleeding. Aliment Pharmacol Ther. 2001;15:575–94. 17. Marrero J, Scheiman J. Prevention of recurrent variceal bleeding: as easy as A.P.C.? Gastointest Endosc. 2002;56:600–3. 18. Asaki S. Efficacy of endoscopic pure ethanol injection method for gastrointestinal ulcer bleeding. World J Surg. 2000;24:294–8. 19. Irisawa A, Obara K, Bhutani M. Role of para-esophageal collateral veins in patients with portal hypertension based on the results of endoscopic ultrasonography and liver scintigraphy analysis. J Gastroenterol Hepatol. 2003;18:309–14. 20. Irisawa A, Saito A, Obara K. Endoscopic recurrence of esophageal varices is associated with the specific EUS abnormalities: severe peri- esophageal collateral veins and large perforating veins. Gastointest Endosc. 2001;53:77–84. 21. Toyonaga A, Iwao T. Paraesophageal collaterals in endoscopic therapies for esophageal varices: good or bad? . J Gastroenterol Hepatol. 2001;16:489–90. 22. Konishi Y, Nakamura T, Kida H, Seno H, Okazaki K, Chiba T. Catheter US probe EUS evaluation of gastric cardia and perigastric vascular structures to predict esophageal variceal recurrence. Gastointest Endosc. 2002;55:197–203. 23. Lahoti S, Catalano M, Alcocer E, Hogan W, Geenen J. Obliteration of esophageal varices using EUS-guided sclerotherapy with color Doppler. Gastrointest Endosc. 2000;51:331–3.
50 24. De Paulo G, Ardengh J, Nakao F, Ferrari A. Treatment of esophageal varices: a randomized controlled trial comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins. Gastointest Endosc. 2006;63:396–402. 25. 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. 26. Sarin SK, Kumar A. Sclerosants for variceal sclerotherapy: a critical appraisal. Am J Gastroenterol. 1990;85:641–9. 27. 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. 28. Rengstorff D, Binmoeller K. A pilot study of 2-octyl cyanoacrylate injection for treatment of gastric fundal varices in humans. Gastointest Endosc. 2004;59:553–8. 29. Boustiere C, Dumas O, Jouffre C, Letard JC, Patouillard B, Etaix JP, et al. Endoscopic ultrasonography classification of gastric varices in patients with cirrhosis. Comparison with endoscopic findings. J Hepatol. 1993;19:268–72. 30. Lee YT, Chan FK, Ng EK, Leung VK, Law KB, Yung MY, et al. EUS-guided injection of cyanoacrylate for bleeding gastric varices. Gastrointest Endosc. 2000;52:168–74. 31. Iwase H, Suga S, Morise K. Color Doppler endoscopic ultrasonography for the evaluation of gastric varices and endoscopic obliteration with cyanoacrylate glue. Gastointest Endosc. 1995;41:150–4. 32. 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. 33. 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;36:710–14. 34. Romero-Castro R, Pellicer-Bautista F, Jime-nez-Saenz M. EUSguided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases. Gastointest Endosc. 2007;66:402–7. 35. Alexander S, Korman MG, Sievert W. Cyanoacrylate in the treatment of gastric varices complicated by multiple pulmonary emboli. Intern Med J. 2006;36:462–5. 36. Kok K, Bond RP, Duncan IC, Fourie PA, Ziady C, van den Bogaerde JB, et al. Distal embolization and local vessel wall ulceration after gastric variceal obliteration with N-butyl-2cyanoacrylate: a case report and review of the literature. Endoscopy. 2004;36:442–6. 37. Dhiman R, Chawla Y, Taneja S. Endoscopic sclerotherapy of gastric variceal bleeding with N-butyl-2-cyanoacrylate. J Clin Gastroenterol. 2002;35:222–7. 38. Bhasin D, Sharma B, Prasad H. Endoscopic removal of sclerotherapy needle from gastric varix after N-butyl-2cyanoacrylate injection. Gastointest Endosc. 2000;51:497–8. 39. Levy M, Wong Kee Song L, Kendrick M. EUS-guided coil embolization for refractory ectopic variceal bleeding. Gastointest Endosc. 2008;67:572–4. 40. 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. 41. Romero-Castro R, Ellrichmann M, Ortiz-Moyano C, Subtil-Inigo JC, Junquera-Florez F, Gornals JB, et al. EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study (with videos). Gastrointest Endosc. 2013;78:711– 21.
J Hepatobiliary Pancreat Sci (2015) 22:44–50 42. Binmoeller K, Weilert F, Shah J, Kim J. EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection. GIE. 2011;74:1019–25. 43. Sanchez-Yague A, Shah J, Nguyen-Tang T. EUS-guided coil embolization of gastric varices after unsuccessful endoscopic glue injection. Gastointest Endosc. 2009;69:A–6. 44. Binmoeller K. Optimizing interventional EUS: the echoendoscope in evolution. Gastointest Endosc. 2007;66:917–19. 45. Armonis A, Patch D, Burroughs A. Hepatic venous pressure measure- ment: an old test as a new prognostic marker in cirrhosis? Hepatology. 1997;25:245–8. 46. Nguyen-Tang T, Shah J, Sanchez-Yague A. Useofthefront-view forward-array echoendoscope to evaluate right colonic subepithelial lesions. Gastointest Endosc. 2010;72:606–10. 47. Magno P, Ko C, Buscaglia J. EUS-guided angiography: a novel approach to diagnostic and therapeutic interventions in the vascular system. Gastointest Endosc. 2007;66:587–91. 48. Lai L, Poneros J, Santilli J. EUS-guided portal vein catheterization and pressure measurement in an animal model: a pilot study of feasibility. Gastointest Endosc. 2004;59:280–3. 49. Giday S, Clarke J, Buscaglia J, Shin E, Ko C, Magno P, et al. EUS-guided portal vein catheterization: a promising novel approach for portal angiography and portal vein pressure measurements. Gastointest Endosc. 2008;67:338–42. 50. D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic view. Hepatology. 1995;22:332–53. 51. 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. 52. Buscaglia J, Dray X, Shin E, Magno P, Chmura K, Surti V, et al. A new alternative for a transjugular intrahepatic portosystemic shunt: EUS-guided creation of an intrahepatic portosystemic shunt (with video). Gastointest Endosc. 2009;69:941–7. 53. Binmoeller K, Shah J. EUS-guided transgastric intrahepatic portosystemic shunt using the axios stent. Gastointest Endosc. 2011;73:A–167. 54. Vazquez-Sequeiros E, Foruny Olcina J. Endoscopic ultrasound guided vascular access and therapy: a promising indication. World J Gastrointest Endosc. 2010;2:198–202. 55. Matthes K, Sahani D, Holalkere N, Mino-Kenudson M, Brugge W. Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx. Acta Gastroenterol Belg. 2005;68:412–15. 56. Fritscher-Ravens A, Ganbari A, Mosse C. Transesophageal endoscopic ultrasound- guided access to the heart. Endoscopy. 2007;39:385–9.
Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: Video S1 Technique of cyanoacrylate glue injection into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. Video S2 Technique of endoscopic ultrasound (EUS)guided coil and glue treatment of large gastric fundal varices.
TOPIC
Endoscopic ultrasound-guided intravascular therapy Kenneth F. Binmoeller · Oriol Sendino · Steven D. Kane
Published online: 4 November 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional endoscopic ultrasound (EUS) has enabled access to these structures with a standard fine-needle aspiration (FNA) needle. Sclerosants, cyanoacrylate, and coils can be delivered through the lumen of the FNA needle. EUS-guided treatment of gastric varices has theoretical advantages over conventional endoscopy-guided treatment. Controlled studies are needed to determine the role of EUS-guided treatment for primary and secondary prevention of variceal bleeding. There is a growing list of novel indications for EUS-guided vascular therapy that include portal vein angiography and pressure measurements, intrahepatic portosystemic shunt placement, and micro coil embolization of vascular structures. Additionally, access and therapy of the heart and surrounding structures appears feasible. Keywords Endoscopic ultrasound · Gastrointestinal bleeding · Vascular access Introduction Vessels have been a target for therapy by interventional radiology for several decades now. Refractory gastrointestinal (GI) bleeding is treated by selective angiographic embolization. Transjugular intrahepatic portosystemic shunt (TIPS) is widely used for refractory bleeding esophageal or gastric varices (GV) associated with portal hypertension [1, 2]. Placement of endovascular grafts is now mainstream and the first reports of trans-aortic valve implantation (TAVI) have emerged [3]. K. F. Binmoeller (*) · O. Sendino · S. D. Kane Paul May and Frank Stein Interventional Endoscopy Services, California Pacific Medical Center, Suite 600, Stanford Building, 2351 Clay Street, San Francisco, CA 94115, USA e-mail: [email protected]
Endoscopic ultrasound (EUS) offers an attractive alternative approach to interventional radiological vascular therapy of vessels in close proximity to the GI tract. Major vascular structures including the heart, aorta, celiac axis, portal vein (PV), hepatic veins, mesenteric vessels, and aberrant vascular shunts such as speno-renal shunts associated with portal hypertension are easily identified. Even smaller vascular structures such as the gastro-duodenal artery, splenic vessels, hepatic artery, and PV branches can be confidently traced and identified.
Non-variceal gastrointestinal bleeding Endoscopic techniques for the treatment of non-variceal GI bleeding include the injection of epinephrine [4–6], thermal contact therapy [7–10], mechanical hemostasis with clips [11], and band ligation [12]. These modalities are well established and effective in the majority of cases, but may fail in up to 15% of cases [13]. EUS-guided vascular therapy was first reported in a case series of five patients, four with refractory bleeding from hemosuccus pancreaticus, a Dieulafoy’s lesion, duodenal ulceration, and a GI stromal tumor (GIST) [14]. These patients had presented with an average of three prior bleeding episodes, required multiple units of packed red blood cells, and repeated endoscopic and vascular therapies, all of which were ineffective. EUS-guided injection therapy of absolute alcohol and/or cyanoacrylate (CYA) was delivered directly into the bleeding vessels. Real-time monitoring by Doppler ultrasound was used to conclude the injection therapy when no visible flow could be seen in the bleeding vessel. Control of the bleeding source was achieved in all of these refractory cases without any complications. We have successfully injected CYA glue into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. The technique is shown in Figure 1, Video S1.
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Fig. 1 Cyanoacrylate glue injection into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. (a) Doppler showing feeder vessel traversing the gastric wall; (b) Glue injection through the fine-needle aspiration needle in feeder vessel
Esophageal variceal bleeding Endoscopic band ligation is well established as the preferred technique for primary and secondary therapy of esophageal varices [15–17]. Injection of sclerosants [18] has been used as rescue therapy when band ligation fails to eradicate varices. Rebleeding after endoscopic therapy is thought to be secondary to failure to treat perforating veins and collateral vessels that feed esophageal varices [19, 20]. EUS enables the visualization of perforating veins and collaterals for targeted sclerotherapy [20–22]. Lahoti et al. [23] first reported the use of EUS-ES to achieve variceal obliteration in 2000. The injection of sclerosant was directed at the perforating vessels until flow was no longer seen. All five treated patients achieved variceal obliteration after an average of 2.2 sessions. No recurrent bleeding was reported after a mean follow-up period of 15 months. De Paulo et al. [24] reported a randomized controlled trial of 50 patients comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins. They found similar rebleeding rates after similar numbers of sessions to achieve obliteration, but rebleeding was found to be significantly associated with the presence of collateral vessels. Currently EUS-guided sclerotherapy of esophageal varices should be reserved for patients with bleeding refractory to band ligation and conventional sclerotherapy.
Gastric variceal bleeding GV are less common than esophageal varices, but may be present in up to 20% of patients with portal hypertension. As many as 65% of GV will bleed over 2 years [25]. The results of variceal ligation for GV have been poor, which is not surprising given the larger size of GV [26]. Direct endoscopic CYA injection of GV, first described by Soehendra and colleagues in the 1980s, is widely considered first-line therapy [27]. N-butyl-2-cyanoacrylate has been used in multiple case series and randomized trials with hemostasis rates
of 58% to 100% and rebleeding rates of 0% to 40% [15]. Our group reported on the use of 2-octyl-cyanoacrylate in 25 patients with GV with similar hemostasis rates and a 4% rebleeding rate over 11 months [28]. The role of EUS in the management of GV is foremost diagnostic. Owing to the location in the deep submucosal layer of the stomach, GV may be difficult to detect or differentiate from prominent gastric folds on endoscopy. Boustiere et al. [29] found that the use of EUS increases the detection of fundal varices six-fold. Even when detected, the visualized portion may be only the tip of the iceberg. Lee et al. [30] demonstrated that performing EUS to monitor GV obliteration after glue injection and performing repeated CYA injections when incompletely obliterated reduced the risk of bleeding with a possible reduction in mortality when compared with “on-demand” injections alone. Similarly, Iwase et al. [31] showed residual patency of treated varices correlated with rebleeding risk after glue injection. Varix obliteration can be confirmed by the absence of blood flow on color Doppler. EUS has conceptual advantages to guide the injection of glue into GV. Endoscopy-guided injection has the limitation that targeting is “blind” and may result in injection adjacent to the varix (paravariceal), missing the varix lumen. Data from sclerotherapy suggests that up to 60% of injections are actually paravariceal [26]. EUS-guided glue injection is attractive as it enables sonographic visualization of glue delivery into the varix lumen. Furthermore, it allows for visualization of deeper varices as well as the feeding vein system, which derives from the left gastric vein trunk, the posterior gastric vein, short gastric vein or outflowing vein system [31, 32] with gastro-renal shunts [33]. Another advantage of EUS-guided treatment is the lack of dependency on direct varix visualization when performing treatment. 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. Romero-Castro et al. [34] described a small case series targeting the “feeder vessel,” rather than the varix lumen proper, under EUS-guidance. The rationale for targeting the
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feeder vessel was to minimize the amount of CYA needed to achieve obliteration of GV and thereby reduce the risk of embolization. The authors targeted the feeder vein using a 1:1 mixture of N-butyl-2-cyanoacrylate and lipiodol. The lipiodol enabled fluoroscopic visualization of the injected vessel and confirmation that it had been accurately targeted. There was no rebleeding or complications observed. It should be noted that the identification of the feeder vessel with EUS can at times be difficult, as was acknowledged by the authors. Further, because the perforating vessel may be afferent or efferent, contrast should be injected prior to treatment to determine directional flow relative to the varix.
EUS-guided coiling A major, potentially life-threatening risk of glue injection of GV is systemic embolization, primarily via highly prevalent splenorenal and gastrorenal portosystemic shunts [35]. Inflammatory reactions to CYA include pain and fever, and local tissue inflammation can result in ulceration [36]. Entrapment of the needle in the varix by glue and damage to scope has also been reported [37, 38]. To avoid complications related to the use of glue, case series have described the deployment of commercially available stainless steel coils to obliterate varices. Most coils used in interventional radiology fit through EUS-fine-needle aspiration (FNA) needles and can be used for EUS-guided therapy. The coils used at our institution are made of Inconel, a nickel-based superalloy. The coil contains radially extending, synthetic fibers that help induce clot and hemostasis. The coils are magnetic resonance imaging (MRI) conditional and can be used in a static magnetic field of 3 Tesla or less. A variety of sizes and lengths are available. A 0.035-inch coil will fit through a 19-gauge FNA needle. Extended length ranges from 2 to 15 cm, with coiled diameter ranging from 2 to 20 mm and approximate number of loops from 1.9 to 5.6. Smaller 0.018-inch coils are also available and will fit through a 22-gauge FNA needle. Coil selection should depend on the size of the varix, but typically a coiled diameter of 10–20 mm is used. In 2008, Levy et al. [39] reported the first case of EUSguided coil injection for acute ectopic gastric variceal bleeding. They advanced a total of three embolization microcoils through a 22-gauge EUS-FNA needle for variceal obliteration. The length of the coil was loaded into the needle hub and advanced to the tip of the needle using a stylet. The varix was punctured with the FNA needle and the stylet was further advanced to deliver the coil. Rebleeding occurred, but was successfully treated with two additional coils placed into untreated varices. Romero-Castro [40] used coils of 0.035-inch diameter, 50–150 mm length, and diameter of
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8–15 mm, deployed through a 19-gauge needle. In one patient with a large gastro-renal shunt the authors failed to achieve obliteration of GV despite deployment of 13 coils. The authors subsequently delivered nine additional coils into the perforating feeding vein. Cost becomes an obvious consideration when using such large numbers of coils to achieve varix obliteration. A recent retrospective trial of 30 patients comparing EUS-guided coil injection to EUS-guided CYA injection revealed similar obliteration rates, but fewer endoscopy sessions were required in the coil group (82% obliteration in a single session compared to 53%) [41]. Of note, the intended therapy was for coil injection in all, but technical difficulties hindering the use of coils were encountered in 19 of 30 patients, resulting in only 11 treated with coils. The rates of adverse events were significantly higher in the CYA vs. the coil group (58% vs. 9%), although nine of the 11 adverse events in the CYA group were asymptomatic pulmonary glue embolisms found on routine postprocedure CT. This conclusion was that glue embolization is likely more common than appreciated, but that it rarely causes symptoms.
EUS-guided cyanoacrylate injection and coiling (Fig. 2, Video S2) Our center has developed an EUS-guided approach consisting of coil placement, immediately followed by glue injection into the same varix. We theorized that the coil provides a scaffold for glue retention at the site of intravariceal injection. Our ex-vivo work has shown that glue immediately adheres to the fibers of a “wool coil” when immersed in a container of heparinized blood [42]. The combination of coil and glue may increase hemostasis and varix obliteration rates while decreasing the risk of embolization. The clinical protocol at our center for combined EUSguided coil and glue is as follows: (1) Standard upper endoscopy to establish candidacy for glue and coil treatment. (2) Prophylactic antibiotics are given. (3) EUS with a curvilinear array echoendoscope and intraluminal water filling of the gastric fundus for improved sonographic visualization. (4) EUS-guided coil placement: The varix is punctured from the distal esophagus or cardia with a 19- or 22-gauge, salineprimed, FNA needle (needle size based on size of coil to be delivered). After puncture, intravariceal needle position is confirmed by blood aspiration or saline injection (bubbles visualized endosonographically). The coil is delivered into the varix by using the needle stylet as a pusher, and can be sonographically visualized as a curved echogenicity. Care is taken to ensure that advancement of the coil does not force the needle back out of the varix lumen. (5) After the coil is deployed, blood is again aspirated to ensure the needle
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Fig. 2 Endoscopic ultrasound (EUS)-guided coil and glue therapy for gastric fundal varices. (a) Fundal varix, with EUS image (insert); (b) deployment of coil (arrow) through the 19-gauge needle; (c) glue and coil complex (arrow) after injection of cyanoacrylate glue through the 19-gauge needle; (d) eradication of fundal varices on 9 months follow-up endoscopy
remains in the lumen of the varix. Undiluted 2-octylcyanoacrylate (1 ml) is immediately injected over 30–45 s, followed by normal saline to flush the glue through the dead space of the catheter. (6) After glue injection, the varix is interrogated with EUS and color Doppler is used to confirm absence of flow. Additionally, switching to a diagnostic gastroscope, the varix can be endoscopically probed in retroflexion with a closed forceps to assess induration. Further injections of aliquots of 1 ml of glue or repeat combination of coil and glue are used as needed for complete obliteration of all varices. If concomitant esophageal varices are seen, conventional band ligation is performed after glue/ coil treatment. We reported our first use of coil and CYA as “rescue” treatment after standard endoscopy-guided CYA treatment failed in a patient with massive gastric fundal variceal (GFV) bleeding [43]. We later reported our experience using a combined approach of CYA injection after deployment of a single coil in a series of 30 patients with GFV. The coil diameter after deployment (up to 20 mm) was selected to approximate that of the lumen of the targeted varix. Combined coil and glue therapy was found to be safe and effective in eradicating gastric fundal varices with only a single treatment session required in 96% of the patients [44]. Immediate hemostasis was achieved in all patients with active bleeding. Rebleeding from incompletely treated GV occurred in one patient; apart from this, there were no adverse events. No patients required surgical or percutaneous shunt procedures. The average volume of CYA (2-octyl-cyanoacrylate) 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 [38]. There was no damage to the echoendoscope related to glue injections and no procedurerelated complications. We have applied the technique of glue and coil injection for the treatment of large bleeding rectal varices [45]. The gastric fundus can be well visualized on EUS with the transducer positioned in the distal esophagus or at the cardia. Since the echoendoscope does not enter into the support, EUS-guided access to GFV 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. We have used both a conventional and a prototype forward view (FV) curved linear array (CLA) echoendoscopes for EUS-guided treatment. We found the FV-CLA instrument to have several technical advantages: (1) more perpendicular needle orientation to the target lesion; (2) uniaxis instrumentation imparting an increased forward transfer of force to the tip of the needle; (3) frontview optics that improve endoscopic visualization; and (4) accessory water jet channel for water filling and irrigation. These advantages have been previously described in other clinical applications of the FV-CLA echoendoscope [44, 46]. Comparative studies are needed to determine the benefit of combined CYA and coil treatment of GV over CYA alone, as well as the advantages of EUS-guidance over endoscopy-guidance.
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Fig. 3 (a) Endoscopic ultrasound view showing placement of dual-flanged metal stent– intrahepatic porto-systemic shunt across inferior vena cava (IVC) and portal vein (PV); (b) Necropsy specimen confirming lumen apposing stent positioning across IVC and PV
Portal vein angiography and pressure measurements PV angiography and pressure measurements can add important clinical information for the management of patients with chronic liver disease and portal hypertension. Direct transcutaneous transhepatic portal pressure measurements are hampered by technical difficulties and a high rate of complications [45]. EUS may permit PV access, contrast injection and monitoring the PV pressure [47]. Direct measurements of the PV pressure under EUS guidance was first reported by Lai et al. [48] in the animal model. A 22-gauge FNA needle was advanced under EUS guidance into the extrahepatic PV and pressure measurements were obtained. Giday performed EUS-guided transhepatic PV catheterization with a modified ERCP catheter, which allowed them to perform portal angiography and obtain continuous portal pressure readings over one hour. Results showed minimal variability within each animal. The position of the catheter inside the PV was stable and was not influenced by the animal’s respiratory or endoscope movement [49]. A transhepatic route for catheter placement into the PV was selected based on the theory that hepatic parenchyma surrounding the catheter will tamponade the track after catheter removal and thereby prevent postprocedural bleeding [49].
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 [1]. The effectiveness of TIPS has been well documented in the treatment of acute variceal bleeding [2, 27], the prevention of recurrent variceal bleeding [50] and the management of refractory ascites [51]. TIPS is
a widely used technique, predominantly performed by interventional radiologists, and limited to tertiary-referral centers. Buscaglia first described EUS-guided creation of an intrahepatic portosystemic shunt (IPS) in a live porcine model [52]. Under direct EUS observation, the HV and the PV were sequentially punctured with a 19-gauge FNA needle following which a guidewire was advanced through the needle into the PV. A self-expandable tubular metal stent was inserted over the guidewire and deployed with its distal end inside the PV and the proximal end inside the HV. All steps of the procedure were clearly seen by EUS. Our group [53] recently reported on the use of a lumenapposing stent in the endoscopic creation of a transgastric IPS. The AXIOS (Xlumena, Mountain View, CA, USA) is a fully coated, dual-flanged metal stent constrained in a 10.5 Fr delivery catheter. When expanded, the flange and body diameters measure 10 mm and 4 mm, respectively. The length of the AXIOS is 8 mm. A therapeutic 3.7 mm working channel echoendoscope was advanced into the stomach of five healthy animals and used to locate the PV and inferior vena cava (IVC). A 0.035 guidewire was advanced and placed into the PV. The needle was then exchanged for the AXIOS delivery catheter. The distal anchor flange of the AXIOS was deployed in the PV and the proximal anchor flange was deployed in the IVC (Fig. 3). Gross necropsy on all animals confirmed stent placement between the PV and IVC and no evidence of tissue injury or hematoma.
Microcoil embolization Interventional radiologists have performed selective embolization of the right branch of the PV to produce compensatory hypertrophy of the left hepatic lobe in patients
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undergoing right hepatectomy. Preliminary results in an animal model [54] suggest EUS-guided coil embolization of the right PV can produce the intended hypertrophy of the left hepatic lobe. Matthes et al. [55] reported on the injection of the polymer (Enteryx) into the main PV, to occlude the vessel. These anecdotal reports in the animal model support a role for EUS-guided delivery of different devices or compounds to occlude small and large vessels. Further studies are needed to determine the potential benefit over percutaneous approaches. Access to the heart The proximity of the heart to the esophagus lends itself to EUS-guided intervention. Fritscher-Ravens et al. [56] described EUS-guided puncture of the heart. In porcine studies, an FNA needle could be introduced repeatedly into the left atrium, followed by the injection of saline. Reaching the aortic valve was thought to be more difficult because of the moving target, but ablation therapy was felt to be technically possible. The coronary artery was successfully punctured in several of the animals. No significant injury was observed in two acute and six survival animals. The authors also reported EUS-guided pericardial fluid aspiration in three patients and puncture of a left atrial mass in a third patient. Conclusion The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional EUS has enabled access to these structures with a standard FNA needle. Sclerosants, CYA and, more recently, coils can be delivered through the lumen of the FNA needle. Data are still very limited and multicenter, prospective controlled trials are needed to show clinical effectiveness and safety in humans. The development of new tools designed for EUS-guided vascular therapy is needed. Conflict of interest
None declared.
References 1. Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol. 2007;41:S344–51. 2. Boyer T, Haskal Z. AASLD practice guideline. The role of transjugular intra-hepatic portosystemic shunt in the management of portal hyper- tension. Hepatology. 2005;41:1–15. 3. Webb J, Cribier A. Percutaneous transarterial aortic valve implantation. Eur Heart J. 2011;32:140–7.
49 4. Lin H, Hsieh Y, Tseng G. A prospective, randomized trial of largeversus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc. 2002;55:615–19. 5. Song S, Chung J, Moon YM. Comparison of the hemostatic effect of endoscopic injection with fibrin glue and hypertonic salineepinephrine for peptic ulcer bleeding: a prospective randomized trial. Endoscopy. 1997;29:827–33. 6. Kubba A, Murphy W, Palmer KR. Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin. Gastroenterology. 1996;111:623–8. 7. Kanai M, Hamada A, Endo Y. Efficacy of argon plasma coagulation in nonvariceal upper gastrointestinal bleeding. Endoscopy. 2004;36:1085–8. 8. Chau C, Siu W, Law B. Randomized controlled trial comparing epinephrine injection plus heat probe coagulation versus epinephrine injection plus argon plasma coagulation for bleeding peptic ulcers. Gastointest Endosc. 2003;57:455–61. 9. Jensen D, Kovacs T, Jutabha R. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology. 2002;123:407– 13. 10. Laine L, Estrada R. Randomized trial of normal saline solution injection versus bipolar electrocoagulation for treatment of patients with high- risk bleeding ulcers: is local tamponade enough? Gastointest Endosc. 2002;55:6–10. 11. Chou Y, Hsu P, Lai K. A prospective, randomized trial of endoscopic hemoclip placement and distilled water injection for treatment of high-risk bleeding ulcers. Gastointest Endosc. 2003;57:324–8. 12. Mumtaz R, Shaukat M, Ramirez F. Outcomes of endoscopic treatment of gastroduodenal Dieulafoy’s lesion with rubber band ligation and thermal/injection therapy. J Clin Gastroenterol. 2003;36:310–14. 13. Longstreth G. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am J Gastrenterol. 1997;92:419–24. 14. Levy M, Wong Kee Song L, Farnell M. Endoscopic ultrasound (EUS)-guided angiotherapy of refractory gastrointestinal bleeding. Am J Gastrenterol. 2008;103:352–9. 15. De Franchis R, Primignani M. Endoscopic treatments for portal hyper- tension. Semin Liver Dis. 1999;19:439–55. 16. Helmy A, Hayes P. Review article: current endoscopic therapeutic options in the management of variceal bleeding. Aliment Pharmacol Ther. 2001;15:575–94. 17. Marrero J, Scheiman J. Prevention of recurrent variceal bleeding: as easy as A.P.C.? Gastointest Endosc. 2002;56:600–3. 18. Asaki S. Efficacy of endoscopic pure ethanol injection method for gastrointestinal ulcer bleeding. World J Surg. 2000;24:294–8. 19. Irisawa A, Obara K, Bhutani M. Role of para-esophageal collateral veins in patients with portal hypertension based on the results of endoscopic ultrasonography and liver scintigraphy analysis. J Gastroenterol Hepatol. 2003;18:309–14. 20. Irisawa A, Saito A, Obara K. Endoscopic recurrence of esophageal varices is associated with the specific EUS abnormalities: severe peri- esophageal collateral veins and large perforating veins. Gastointest Endosc. 2001;53:77–84. 21. Toyonaga A, Iwao T. Paraesophageal collaterals in endoscopic therapies for esophageal varices: good or bad? . J Gastroenterol Hepatol. 2001;16:489–90. 22. Konishi Y, Nakamura T, Kida H, Seno H, Okazaki K, Chiba T. Catheter US probe EUS evaluation of gastric cardia and perigastric vascular structures to predict esophageal variceal recurrence. Gastointest Endosc. 2002;55:197–203. 23. Lahoti S, Catalano M, Alcocer E, Hogan W, Geenen J. Obliteration of esophageal varices using EUS-guided sclerotherapy with color Doppler. Gastrointest Endosc. 2000;51:331–3.
50 24. De Paulo G, Ardengh J, Nakao F, Ferrari A. Treatment of esophageal varices: a randomized controlled trial comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins. Gastointest Endosc. 2006;63:396–402. 25. 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. 26. Sarin SK, Kumar A. Sclerosants for variceal sclerotherapy: a critical appraisal. Am J Gastroenterol. 1990;85:641–9. 27. 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. 28. Rengstorff D, Binmoeller K. A pilot study of 2-octyl cyanoacrylate injection for treatment of gastric fundal varices in humans. Gastointest Endosc. 2004;59:553–8. 29. Boustiere C, Dumas O, Jouffre C, Letard JC, Patouillard B, Etaix JP, et al. Endoscopic ultrasonography classification of gastric varices in patients with cirrhosis. Comparison with endoscopic findings. J Hepatol. 1993;19:268–72. 30. Lee YT, Chan FK, Ng EK, Leung VK, Law KB, Yung MY, et al. EUS-guided injection of cyanoacrylate for bleeding gastric varices. Gastrointest Endosc. 2000;52:168–74. 31. Iwase H, Suga S, Morise K. Color Doppler endoscopic ultrasonography for the evaluation of gastric varices and endoscopic obliteration with cyanoacrylate glue. Gastointest Endosc. 1995;41:150–4. 32. 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. 33. 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;36:710–14. 34. Romero-Castro R, Pellicer-Bautista F, Jime-nez-Saenz M. EUSguided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases. Gastointest Endosc. 2007;66:402–7. 35. Alexander S, Korman MG, Sievert W. Cyanoacrylate in the treatment of gastric varices complicated by multiple pulmonary emboli. Intern Med J. 2006;36:462–5. 36. Kok K, Bond RP, Duncan IC, Fourie PA, Ziady C, van den Bogaerde JB, et al. Distal embolization and local vessel wall ulceration after gastric variceal obliteration with N-butyl-2cyanoacrylate: a case report and review of the literature. Endoscopy. 2004;36:442–6. 37. Dhiman R, Chawla Y, Taneja S. Endoscopic sclerotherapy of gastric variceal bleeding with N-butyl-2-cyanoacrylate. J Clin Gastroenterol. 2002;35:222–7. 38. Bhasin D, Sharma B, Prasad H. Endoscopic removal of sclerotherapy needle from gastric varix after N-butyl-2cyanoacrylate injection. Gastointest Endosc. 2000;51:497–8. 39. Levy M, Wong Kee Song L, Kendrick M. EUS-guided coil embolization for refractory ectopic variceal bleeding. Gastointest Endosc. 2008;67:572–4. 40. 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. 41. Romero-Castro R, Ellrichmann M, Ortiz-Moyano C, Subtil-Inigo JC, Junquera-Florez F, Gornals JB, et al. EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study (with videos). Gastrointest Endosc. 2013;78:711– 21.
J Hepatobiliary Pancreat Sci (2015) 22:44–50 42. Binmoeller K, Weilert F, Shah J, Kim J. EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection. GIE. 2011;74:1019–25. 43. Sanchez-Yague A, Shah J, Nguyen-Tang T. EUS-guided coil embolization of gastric varices after unsuccessful endoscopic glue injection. Gastointest Endosc. 2009;69:A–6. 44. Binmoeller K. Optimizing interventional EUS: the echoendoscope in evolution. Gastointest Endosc. 2007;66:917–19. 45. Armonis A, Patch D, Burroughs A. Hepatic venous pressure measure- ment: an old test as a new prognostic marker in cirrhosis? Hepatology. 1997;25:245–8. 46. Nguyen-Tang T, Shah J, Sanchez-Yague A. Useofthefront-view forward-array echoendoscope to evaluate right colonic subepithelial lesions. Gastointest Endosc. 2010;72:606–10. 47. Magno P, Ko C, Buscaglia J. EUS-guided angiography: a novel approach to diagnostic and therapeutic interventions in the vascular system. Gastointest Endosc. 2007;66:587–91. 48. Lai L, Poneros J, Santilli J. EUS-guided portal vein catheterization and pressure measurement in an animal model: a pilot study of feasibility. Gastointest Endosc. 2004;59:280–3. 49. Giday S, Clarke J, Buscaglia J, Shin E, Ko C, Magno P, et al. EUS-guided portal vein catheterization: a promising novel approach for portal angiography and portal vein pressure measurements. Gastointest Endosc. 2008;67:338–42. 50. D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic view. Hepatology. 1995;22:332–53. 51. 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. 52. Buscaglia J, Dray X, Shin E, Magno P, Chmura K, Surti V, et al. A new alternative for a transjugular intrahepatic portosystemic shunt: EUS-guided creation of an intrahepatic portosystemic shunt (with video). Gastointest Endosc. 2009;69:941–7. 53. Binmoeller K, Shah J. EUS-guided transgastric intrahepatic portosystemic shunt using the axios stent. Gastointest Endosc. 2011;73:A–167. 54. Vazquez-Sequeiros E, Foruny Olcina J. Endoscopic ultrasound guided vascular access and therapy: a promising indication. World J Gastrointest Endosc. 2010;2:198–202. 55. Matthes K, Sahani D, Holalkere N, Mino-Kenudson M, Brugge W. Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx. Acta Gastroenterol Belg. 2005;68:412–15. 56. Fritscher-Ravens A, Ganbari A, Mosse C. Transesophageal endoscopic ultrasound- guided access to the heart. Endoscopy. 2007;39:385–9.
Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: Video S1 Technique of cyanoacrylate glue injection into the feeder artery of a bleeding Dieulafoy lesion to stop refractory bleeding. Video S2 Technique of endoscopic ultrasound (EUS)guided coil and glue treatment of large gastric fundal varices.
