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EUS-guided splenic artery embolization for variceal hemorrhage: balancing creativity and innovation in Endo-hepatology with caution

Published:November 18, 2021DOI:https://doi.org/10.1016/j.gie.2021.09.016

      Abbreviations:

      IR (interventional radiology), PSE (partial splenic embolization), TIPS (transjugular intrahepatic portosystemic shunt)
      The past decade has seen the development and evolution of Endo-hepatology, an exciting field that represents the intersection between endoscopy and liver disease.
      • Samarasena J.
      • Chang K.J.
      Endo-hepatology: a new paradigm.
      The refinement of diagnostic tools including EUS-guided liver biopsy, portal pressure gradient measurement, and shear wave elastography as well as therapeutic interventions for gastroesophageal varices have empowered endoscopists to partner with hepatologists to provide comprehensive care for patients with complex liver disease.
      Esophageal variceal hemorrhage is primarily managed with endoscopic band ligation, but the preferred management strategy of gastric variceal hemorrhage is often less clear. The endoscopic options for gastroesophageal varices-1 include band ligation and direct injection of cyanoacrylate glue through a sclerotherapy needle.
      • Hwang J.H.
      • Shergill A.K.
      • Acosta R.D.
      • et al.
      The role of endoscopy in the management of variceal hemorrhage.
      The 2017 guidelines of the American Association for the Study of Liver Diseases recommend transjugular intrahepatic portosystemic shunt (TIPS) as the treatment of choice for isolated gastric varices-1 or gastroesophageal varices-2 with other options including balloon-occluded retrograde transvenous obliteration or coil-assisted retrograde transvenous obliteration, with the caveat that glue injection can be performed where TIPS is not available.
      • Garcia-Tsao G.
      • Abraldes J.G.
      • Berzigotti A.
      • et al.
      Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases.
      However, these guidelines may need updating in light of recent strong outcomes data with EUS-guided therapies. EUS has improved the treatment of gastric varices over conventional endoscopy by several means: (1) directly confirming intravascular access, (2) allowing the occasional identification of a feeder vessel for even more targeted therapy, (3) allowing controlled injection of both liquid and nonliquid hemostatic agents (such as embolization coils), and (4) providing real-time feedback regarding hemostasis via Doppler flow. The use of EUS-placed embolization coils has been shown to be highly successful and safe compared with standard endoscopic glue injection.
      • Bazarbashi 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.
      Furthermore, EUS combination therapy with glue plus coils has shown even higher clinical success rates, with a low risk of recurrent bleeding or reintervention.
      • McCarty 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.
      However, these procedures are typically limited to expert centers with experienced endoscopists. Although most acute variceal bleeding can be stopped, interventions such as banding or coils/glue can trigger hemodynamic changes and even worsen portal hypertension. Furthermore, there are still cases of refractory variceal bleeding that are anxiety provoking and often require thinking outside the box.
      Zhang et al
      • Zhang Z.-g.
      • Li Z.
      • Yang Y.
      • et al.
      Hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video).
      report their initial experience with a novel technique of EUS-guided partial splenic embolization (PSE) combined with therapy for bleeding gastroesophageal varices to both address the bleeding and mitigate the changes in portal pressure.
      • Zhang Z.-g.
      • Li Z.
      • Yang Y.
      • et al.
      Hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video).
      The series included 5 patients with Child Pugh A liver disease. With the EUS endoscope in the stomach/greater curvature, intravascular puncture was performed with a 19-gauge needle into the splenic arterial branch outside the gut wall in a parahilar location. The coil was then delivered, followed by injection of cyanoacrylate glue with Doppler confirmation of complete obliteration of the vessel. Efficacy was measured by changes in hematologic parameters, and meaningful increases were seen in mean white blood cell count (27,000 to 58,000/L) and platelets (53,000 to 96,000/L). All patients underwent multidetector CT portal venography within 48 hours of presentation as well as 5 days after intervention to evaluate their anatomy and the impact on the hemodynamics of the portosystemic collaterals. After PSE, the mean diameter of the left gastric vein, short gastric vein, and azygous vein all decreased, which is a proxy for reduced risk of variceal bleeding. All patients had minor abdominal pain and fever, but there were no splenic abscesses (all received prophylactic antibiotics), 4 experienced splenic vein thrombosis, and 2 had new ascites.
      The authors should be commended for their creativity, innovation, and diligence. Their EUS approach and technique demonstrated a tremendous knowledge of the vasculature and anatomy. Because their outcomes appear to correlate with the drainage routes of varices, this comprehensive understanding of the anatomy appears critical for performing these interventions. They demonstrate the feasibility and safety of a transgastric puncture to achieve a 65% splenic embolization rate with no bleeding events.
      EUS-guided intravascular therapies have tremendous potential, although they should be approached with caution until larger studies confirm the safety of puncture into a high-pressure arterial system. Interestingly, they also demonstrate a fairly quick natural adaptation of splenic collateralization, which may in fact limit the long-term durability of this procedure, warranting further investigation.
      With a growing body of literature supporting EUS-placed embolization coils and glue for gastric varices, and well-established backup options from interventional radiology (IR), are the current therapies for gastroesophageal variceal hemorrhage sufficient? Is there even a need to talk about additional options? It is helpful to consider the historical context of this procedure, as performed by IR, to better understand the potential role for EUS-guided PSE. Splenic artery embolization has a clear role in splenic injury/trauma, but its utility in hypersplenism with resultant cytopenia is less defined. In the setting of cirrhosis or portal/hepatic vein thrombosis with portal hypertension, the proposed mechanism of action is decreased blood flow through the spleen, leading to less outflow through the splenic vein and a theoretical decrease in portal pressure. Therefore, IR has considered PSE for refractory variceal bleeding or ascites, even in combination with TIPS. Physiologic studies indicate that PSE immediately reduces the hepatic venous pressure gradient, with sustained decreases at 6 months, and the magnitude of change appears related to the amount of splenic necrosis.
      • Zhao Y.
      • Guo L.
      • Huang Q.
      • et al.
      Observation of immediate and mid-term effects of partial spleen embolization in reducing hepatic venous pressure gradient.
      Significant improvements in hematologic parameters are reported after PSE in patients with liver disease; however, the rate of severe adverse events is as high as 15%, with the most common being splenic/portal vein thrombosis and splenic abscess, which can be fatal.
      • N'Kontchou G.
      • Seror O.
      • Bourcier V.
      • et al.
      Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients.
      • Zhu K.
      • Meng X.
      • Qian J.
      • et al.
      Partial splenic embolization for hypersplenism in cirrhosis: a long-term outcome in 62 patients.
      • DuBois B.
      • Mobley D.
      • Chick J.F.B.
      • et al.
      Efficacy and safety of partial splenic embolization for hypersplenism in pre- and post-liver transplant patients: a 16-year comparative analysis.
      The feared adverse event of splenic abscess is particularly problematic in patients awaiting liver transplantation, although some studies suggest that prophylactic antibiotic use might decrease the risk. The IR literature consists mostly of small case series demonstrating improvements in laboratory values; however, serious negative outcomes have occurred at unacceptably high rates. Therefore, IR-performed PSE has been reserved for truly refractory, challenging clinical cases and is performed with caution.
      More recently, this question was addressed in a larger multicenter randomized controlled trial of 108 patients with cirrhosis, hypersplenism, and variceal hemorrhage. Patients who underwent IR-guided PSE combined with endoscopic therapy had lower rates of rebleeding at 2 years (16% vs 31%, P < .001) and improvements in hematologic parameters.
      • Sun X.
      • Zhang A.
      • Zhou T.
      • et al.
      Partial splenic embolization combined with endoscopic therapies and NSBB decreases the variceal rebleeding rate in cirrhosis patients with hypersplenism: a multicenter randomized controlled trial.
      Although most patients had fever and abdominal pain, there were no serious adverse events. This study may provide some reassurance compared with prior data.
      With this background, the major question is whether there is truly an indication for PSE or whether safety is a limitation. Performing EUS-guided PSE takes some degree of courage, given the high rate of adverse events in the IR literature. The present study does not comment on whether other cases of EUS-guided PSE have been performed and not reported. This series provides an excellent starting point, but additional issues need to be addressed, including (1) which anatomy is most conducive to procedural success and how many sessions are needed, (2) how does one predict which patients will have refractory bleeding after variceal therapy and might need adjunct interventions, (3) how do we select patients who would benefit most from PSE, and (4) which approach, EUS or IR, is optimal. There is, in fact, so much variation in patient presentation and vasculature that it might be difficult to develop a standardized approach.
      Although EUS-guided PSE may be the next addition to our Endo-hepatology toolbox, innovation in endoscopy should also be approached with caution. Even if this approach is technically feasible, we need to carefully refine the criteria for indication and determine the value and safety of offering this novel EUS-guided procedure to our patients. Furthermore, collaboration with our IR colleagues will be imperative to the successful and safe growth of EUS-guided vascular therapies related to Endo-hepatology.

      Disclosure

      Dr Samarasena is a consultant for Olympus, Medtronic, Pentax, Conmed, Steris, Pathfinder, Microtech, and Mauna Kea; has an ownership in Docbot; and is the recipient of grants from Cook Medical and ConMed. The other author disclosed no financial relationships.

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      Linked Article

      • Hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video)
        Gastrointestinal EndoscopyVol. 95Issue 1
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          We previously reported a new and combined EUS-guided intervention in a patient with portal hypertension, consisting of obliteration of varices and partial splenic embolization (PSE). Performing PSE is known to diminish the increase in portal venous pressure after endoscopic intervention for varices. The aim of this study was to use multidetector CT portal venography to evaluate the anatomy of esophagogastric varices (EGV) and the impact on hemodynamics of portosystemic collaterals shortly after the concomitant procedures.
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