AGA Clinical Practice Update on Interventional EUS for Vascular Investigation and Therapy: Commentary

Abstract

DescriptionThe purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound–guided vascular investigation and therapies.MethodsThis Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in endoscopic ultrasound–guided vascular investigation and therapy. The purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound–guided vascular investigation and therapies. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in endoscopic ultrasound–guided vascular investigation and therapy. The first endoscopic ultrasound (EUS)–guided vascular intervention was reported in 2000 and evaluated the utility of EUS for sclerotherapy of esophageal varices.1Lahoti S. Catalano M.F. Alcocer E. et al.Obliteration of esophageal varices using EUS-guided sclerotherapy with color Doppler.Gastrointest Endosc. 2000; 51: 331-333Abstract Full Text Full Text PDF PubMed Google Scholar Currently, the most widely utilized EUS-guided vascular interventions include gastric variceal therapy and portosystemic pressure gradient (PPG) measurements. Emerging interventions include treatment of ectopic and rectal varices, splenic artery embolization, therapy of arterial bleeding including pseudoaneurysms, and portal venous sampling. Additional experimental EUS-guided vascular interventions include portosystemic shunt creation. This review of EUS-guided vascular investigation and therapy aims to critically evaluate the evidence for these interventions, examine opportunities for future research, and identify clinical scenarios that may be considered for EUS-directed therapy. This article is not a formal systematic review, but rather is based on a literature review to provide practical advice. No formal rating of the quality of evidence or strength of recommendation was performed. Although less prevalent than esophageal varices, gastric variceal hemorrhage is often more severe and associated with higher mortality.2Sarin S.K. Lahoti D. Saxena S.P. et al.Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.Hepatology. 1992; 16: 1343-1349Crossref PubMed Scopus (885) Google Scholar In particular, endoscopic treatment of bleeding cardiofundal varices (isolated gastric varices type 1 and gastroesophageal varices type 2) tends to be very challenging due to their larger size and location.3Henry Z. Patel K. Patton H. et al.AGA Clinical Practice Update on management of bleeding gastric varices: expert review.Clin Gastroenterol Hepatol. 2021; 19: 1098-1107.e1Abstract Full Text Full Text PDF PubMed Google Scholar Direct endoscopic injection (DEI) of these varices with cyanoacrylate glue is the most widely utilized modality for immediate hemostasis, but treatment requires a clear field of view during endoscope retroflexion, and intravascular needle placement may be inaccurate. Gastric variceal injection therapy under EUS guidance confers potential advantages over conventional endoscopic visualization. EUS enhances the precision of injection (ie, during acute bleeding when direct visualization is impaired) and expands available treatment options (ie, hemostatic coils). Additionally, EUS uses Doppler interrogation to provide real-time feedback of hemostasis. Based on initial experience with DEI, the original choice of injectate for EUS guidance was cyanoacrylate glue. At least 1 retrospective comparative study has shown EUS-guided cyanoacrylate injection to be superior to DEI.4Bick B.L. Al-Haddad M. Liangpunsakul S. et al.EUS-guided fine needle injection is superior to direct endoscopic injection of 2-octyl cyanoacrylate for the treatment of gastric variceal bleeding.Surg Endosc. 2019; 33: 1837-1845Crossref PubMed Scopus (36) Google Scholar To improve hemostasis and decrease adverse events, hemostatic coils designed for use by interventional radiology (IR) were subsequently used in conjunction with EUS-guided cyanoacrylate injection. These coils (Supplementary Figure 1) are constructed from soft platinum wires with spaced synthetic fibers, and placement within the vessel is postulated to initiate thrombus formation. The most published current technique is injection of 1–3 coils (usually Nester or MReye embolization coils; Cook Medical, Bloomington, IN) within the gastric varices to provide a scaffold onto which an adjunct, such as cyanoacrylate, can be subsequently injected to potentially minimize postprocedure embolic events. Figure 1 and Supplementary Video 1 demonstrate the technique for EUS-guided gastric variceal therapy. Prior to treatment, the patient is intubated and placed in the left lateral decubitus position. About 100–200 cm3 of water is instilled through the echoendoscope and retained in the gastric fundus to enhance the delineation of intramural vessels (ie, gastric varices) from extramural collaterals and perforator vein(s), the latter identified by tracing the extramural vessels across the muscularis propria into the intramural varix. A 22-gauge or 19-gauge fine needle aspiration needle is used to access the gastric varix using a transesophageal or transgastric approach. When utilized, 1 or more coils are sequentially placed into the targeted vessel. Of note, there are no definitive data regarding whether the varix itself or the perforator vein(s) should be targeted. Doppler interrogation during coil placement can be used to guide the number of coils required. Fluoroscopy with or without varicealography can be helpful, particularly early in the learning curve, but is not required. When there is a significant reduction or near-absent Doppler flow, an adjunctive agent such as cyanoacrylate can be injected. The multiple steps involved in this technique require adequate training of nurses and technicians. Repeat treatment of other varices can be performed as required. There is growing evidence to support EUS-based gastric variceal therapies over DEI for improved control of acute bleeding, durability of hemostasis, and lower complication rates. For EUS-based therapies, 3 retrospective series5Bhat Y.M. Weilert F. Fredrick R.T. et al.EUS-guided 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: 1164-1172Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 6Binmoeller K.F. Weilert F. Shah J.N. et al.EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection (with videos).Gastrointest Endosc. 2011; 74: 1019-1025Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 7Fujii-Lau L.L. Law R. Song L.M.W.K. et al.Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices.Surg Endosc. 2016; 30: 1396-1404Crossref PubMed Scopus (50) Google Scholar and 2 small randomized controlled trials8Robles-Medranda C. Oleas R. Valero M. et al.Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trial.Endoscopy. 2020; 52: 268-275Crossref PubMed Scopus (42) Google Scholar,9Ribeiro de Almeida Lôbo M. Chaves D.M. Moura D.T.H.D.E. et al.Safety and efficacy of EUS-guided coil plus cyanoacrylate versus conventional cyanoacrylate technique in the treatment of gastric varices: a randomized controlled trial.Arq Gastroenterol. 2019; 56: 99-105Crossref PubMed Scopus (29) Google Scholar have shown very high (∼99%) rates of technical success and control of bleeding and low rates of rebleeding (0%–16%) and adverse events (0%–7%). One recent meta-analysis suggested that any EUS-guided therapy was superior to DEI, with similar treatment efficacy of 94% vs 91%, respectively, but gastric variceal obliteration of 84% vs 63%, respectively (P = .02). Additionally, in subgroup analyses, EUS-guided combination therapy with coils and glue had significantly fewer recurrences (5%) than treatment with glue or coils alone. Another recent meta-analysis also showed EUS-guided combination therapy (coil + glue) to be the preferred strategy, due to hemostasis of 96%–98% and adverse event rates of 10% compared with EUS-guided monotherapy with glue alone (96% and 21%, respectively) and coils alone (90% and 3%, respectively).10McCarty T.R. Bazarbashi A.N. Hathorn K.E. et al.Combination therapy versus monotherapy for EUS-guided management of gastric varices: A systematic review and meta-analysis.Endosc Ultrasound. 2020; 9: 6-15Crossref PubMed Scopus (49) Google Scholar,11Mohan B.P. Chandan S. Khan S.R. et al.Efficacy and safety of endoscopic ultrasound-guided therapy versus direct endoscopic glue injection therapy for gastric varices: systematic review and meta-analysis.Endoscopy. 2020; 52: 259-267Crossref PubMed Scopus (30) Google Scholar Other adjuncts like absorbable gelatin sponge (GELFOAM; Pfizer, New York, NY) in lieu of cyanoacrylate have also shown encouraging results with similar low rebleeding rates and reintervention rates when used in conjunction with coils.12Bazarbashi A.N. Wang T.J. Jirapinyo P. et al.Endoscopic ultrasound-guided coil embolization with absorbable gelatin sponge appears superior to traditional cyanoacrylate injection for the treatment of gastric varices.Clin Transl Gastroenterol. 2020; 11e00175Crossref PubMed Scopus (13) Google Scholar,13Bazarbashi A.N. Wang T.J. Thompson C.C. et al.Endoscopic ultrasound-guided treatment of gastric varices with coil embolization and absorbable hemostatic gelatin sponge: a novel alternative to cyanoacrylate.Endosc Int Open. 2020; 8: E221-E227Crossref PubMed Google Scholar EUS-guided thrombin injection for gastric varices has also been reported in a small series.14Frost J.W. Hebbar S. EUS-guided thrombin injection for management of gastric fundal varices.Endosc Int Open. 2018; 6: E664-E668Crossref PubMed Google Scholar Supplementary Table 1 summarizes the literature for EUS-based gastric variceal therapy. As use of EUS-guided injection therapy of gastric varices increases, certain issues merit investigation and clarification. First, the treatment technique is heterogeneous, including the choice of targeted vessel (intramural varix or perforator vein), the size and number of coils, and the type of injectate used. The development of a consensus technique would be helpful. Second, larger multicenter studies are required to confirm the technical success, safety, and durability of hemostasis and generalizability across centers that offer this modality. Third, additional randomized controlled trials comparing EUS vs other therapies (in particular, IR endovascular therapies such as balloon-assisted retrograde transvenous obliteration and transjugular intrahepatic portosystemic shunt) would help delineate the role of EUS-guided gastric variceal therapies relative to other treatment options. Importantly, these treatment decisions should continue to be made in a multidisciplinary setting with hepatology and IR, to identify optimal cases for IR or endoscopic therapy. Fourth, should EUS-based therapy be offered for primary prophylaxis or only for acute bleeding and secondary prophylaxis? Finally, there are questions about how endosonographers should be trained in EUS injection therapy of gastric varices, which of note is not currently Food and Drug Administration approved, and whether this might include formal didactic and hands-on training sessions or even a mentorship program, given the infrequency of bleeding gastric varices outside of large referral centers. Portal hypertension develops with liver disease and can result most commonly in variceal bleeding, ascites, and encephalopathy. The hepatic venous pressure gradient (HVPG), performed by interventional radiologists, indirectly measures the portal pressure gradient and is defined as the difference between the free hepatic vein pressure and wedged hepatic vein pressure. An HVPG >10 mm Hg is correlated with the development of esophageal varices, whereas an HVPG >12 mm Hg is associated with an increased risk of bleeding esophageal varices. Measurement of wedged hepatic vein pressure has several drawbacks, which include (1) the required use of radiation and contrast and (2) its indirect nature, which can lead to a misdiagnosis of noncirrhotic/presinusoidal portal hypertension.15Kim M.Y. Baik S.K. Suk K.T. et al.[Measurement of hepatic venous pressure gradient in liver cirrhosis: relationship with the status of cirrhosis, varices, and ascites in Korea].Korean J Hepatol. 2008; 14: 150-158Crossref PubMed Scopus (18) Google Scholar, 16Paik Y.H. [The relation between hepatic venous pressure gradient and complications of liver cirrhosis].Korean J Hepatol. 2008; 14: 136-138Crossref PubMed Scopus (1) Google Scholar, 17Wadhawan M. Dubey S. Sharma B.C. et al.Hepatic venous pressure gradient in cirrhosis: correlation with the size of varices, bleeding, ascites, and child's status.Dig Dis Sci. 2006; 51: 2264-2269Crossref PubMed Scopus (68) Google Scholar EUS-guided PPG (EUS-PPG) is a novel technique that allows measurement of the direct hepatic vein portal pressure gradient and is performed with the Food and Drug Administration–approved EchoTip Insight system (Cook Medical, Winston-Salem, NC). EUS-PPG is performed with the patient supine, preferably under general anesthesia, to minimize movement. One dose of prophylactic antibiotics (eg, ciprofloxacin or cefazolin) is usually administered. The compact manometer is first leveled at the midaxillary line/level of the right heart and kept at this level for the remainder of the procedure. Using a linear echoendoscope, the hepatic veins are identified anatomically and confirmed by Doppler (Supplementary Video 2). The middle or left hepatic vein is targeted with a 25-gauge needle via a transgastric approach (Figure 2A). A minimum of 3 consecutive pressure measurements (using a one-needle-stick approach) are taken, and the average measurement is calculated. The intrahepatic portal vein is then identified and confirmed by Doppler (Figure 2B), after which pressure measurements are repeated as described previously. The EUS-PPG is then calculated by subtracting the mean hepatic pressure from the mean portal pressure. There have been several prior studies demonstrating the safety and efficacy of EUS-PPG. In 2014, EUS-PPG was performed successfully on the first human patient.18Fujii-Lau L.L. Leise M.D. Kamath P.S. et al.Endoscopic ultrasound-guided portal-systemic pressure gradient measurement.Endoscopy. 2014; 46: E654-E656Crossref PubMed Google Scholar A subsequent case series by Huang et al19Huang J.Y. Samarasena J.B. Tsujino T. et al.EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study.Gastrointest Endosc. 2017; 85: 996-1001Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar demonstrated an excellent correlation between HVPG measurements obtained by EUS-PPG and the endoscopic findings of portal hypertension in 28 patients with suspected cirrhosis. Additionally, in a single-center retrospective study of 64 patients with chronic liver disease who underwent EUS-PPG and liver biopsy, there was an excellent correlation between EUS-PPG measurements and histologic hepatic fibrosis stage, clinical portal hypertension, thrombocytopenia, splenomegaly, aspartate aminotransferase-to-platelet ratio index score >2, and Fibrosis-4 score >3.25.20Choi A.Y. Chang K.J. Samarasena J.B. et al.Endoscopic ultrasound-guided porto-systemic pressure gradient measurement correlates with histological hepatic fibrosis.Dig Dis Sci. 2022; 67: 5685-5692Crossref PubMed Scopus (2) Google Scholar There were no reported adverse events. The same group published a series of 83 patients and noted that EUS-PPG correlated well with clinical markers of portal hypertension, such as thrombocytopenia and varices.21Choi A.Y. Kolb J. Shah S. et al.Endoscopic ultrasound-guided portal pressure gradient with liver biopsy: 6 years of endo-hepatology in practice.J Gastroenterol Hepatol. 2022; 37: 1373-1379Crossref PubMed Scopus (8) Google Scholar Again, no adverse events were reported. Performing EUS-PPG also improves clinical efficiency, given the concurrent ability to perform esophagogastroduodenoscopy and EUS as a one-stop shop during which PPG, liver biopsy, and endoscopic features of portal hypertension (esophageal varices, portal hypertensive gastropathy) can all be evaluated, obtained, and potentially treated during a single procedure.22Hajifathalian K. Westerveld D. Kaplan A. et al.Simultaneous EUS-guided portosystemic pressure measurement and liver biopsy sampling correlate with clinically meaningful outcomes.Gastrointest Endosc. 2022; 95: 703-710Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar EUS-PPG may be or clinically when patients with data regarding the or of portal hypertension (eg, thrombocytopenia, splenomegaly, HVPG but portal to a patient with or suspected or to or other the is and investigation is to the of portal hypertension mm and clinically significant portal hypertension mm might when using an EUS or standard endovascular approach. The type of used during the as to used for transjugular HVPG might also the measurements of the hepatic vein pressure and portal vein pressure. trials comparing the safety and utility of EUS-PPG vs is varices may secondary to portal hypertension, venous vascular or other of use of EUS to rectal or vessels with coils, or cyanoacrylate are to single case A.N. Thompson C.C. M. the perforator EUS-guided coil embolization for the treatment of bleeding rectal 2020; Full Text Full Text PDF PubMed Scopus (2) Google Sharma R. R. rectal variceal bleeding treated with EUS-guided coil Ultrasound. 2021; PubMed Scopus (2) Google Scholar EUS-guided treatment of ectopic varices has also been described Video L.L. Law R. Song L.M.W.K. et al.Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices.Surg Endosc. 2016; 30: 1396-1404Crossref PubMed Scopus (50) Google Scholar described glue injection with or without coils for = or = varices. series EUS-guided interventions for these are In patients with and variceal bleeding, splenic embolization by interventional splenic and splenic vein and portal pressure. et Z. et through a novel endoscopic intervention in management of varices and (with video).Gastrointest Endosc. 2022; 95: Full Text Full Text PDF PubMed Scopus Google Scholar recently reported using of endoscopic variceal and EUS-guided injection of cyanoacrylate coils to portal hypertension, and recent variceal bleeding in patients had and after treatment, but no splenic were portal and showed a reduction in vein in and a mean splenic embolization of multidisciplinary research is required to vascular and choice of an endoscopic or approach should be utilized for splenic embolization in these are of within a or vascular result from or other and may on or with or of or is usually may be due to or vessel et P. H. A. et al.Endoscopic ultrasound-guided coil and glue for treatment of splenic artery on the Int Open. 2018; 6: PubMed Google Scholar described EUS-guided injection of coils and glue in 6 patients with splenic artery size after success (coil and glue was in all patients without adverse events, and of all 6 was at P. H. A. et al.Endoscopic ultrasound-guided coil and glue for treatment of splenic artery on the Int Open. 2018; 6: PubMed Google Scholar et S. Sharma Sharma D. et al.Endoscopic ultrasound-guided thrombin a management approach for artery Int Open. 2020; 8: PubMed Google Scholar reported EUS-guided injection of thrombin in patients with size of the splenic artery = left hepatic artery = and artery = 1) who were to success was and 2 patients postprocedure At EUS at obliteration was in of and was noted in 1 of S. Sharma Sharma D. et al.Endoscopic ultrasound-guided thrombin a management approach for artery Int Open. 2020; 8: PubMed Google Scholar These case series the utility of EUS-guided treatment of artery or multicenter studies therapy or use as primary or initial treatment for are The portal the venous from the system and of vascular to the In portal may be with and not in venous due to hepatic and In small clinical EUS-guided portal venous sampling has been shown to be and M. ultrasound-guided sampling and of portal in human patients for research studies and J 2020; PubMed Google Scholar In a single-center study of patients with suspected of portal compared with of the potential for portal biopsy to study the of P. et of portal venous from patients with by endoscopic Full Text Full Text PDF PubMed Scopus Google Scholar IR of a hypertensive portal system as a transjugular intrahepatic portosystemic this an endovascular is placed to the hepatic and portal studies have successfully demonstrated that a similar can be via EUS to as a portosystemic et alternative for a transjugular intrahepatic portosystemic EUS-guided of an intrahepatic portosystemic shunt (with video).Gastrointest Endosc. Full Text Full Text PDF PubMed Scopus (68) Google M. H. et al.EUS-guided intrahepatic portosystemic shunt with direct portal pressure a novel alternative to transjugular intrahepatic portosystemic Endosc. 2017; 85: Full Text Full Text PDF PubMed Scopus Google Scholar development of this for patient would require a endovascular with EUS and clinical scenarios in which an EUS approach over an IR approach. There are 2 to demonstrate the clinical utility of EUS-guided vascular The first is a vascular in or the which may an to an endoscopic rather than The is demonstrating a clinical efficacy and safety not to current

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