EUS-guided Glue Injection for Varices Study
Condition: Gastroesophageal Varices
MeSH terms: Varicose Veins
Study type: Interventional

Summary: 
      Bleeding from gastroesophageal varices is one of the major complications of cirrhosis. After
      successful treatment of the acute bleeding episode, patients who do not receive follow-up
      treatment to prevent rebleeding were reported to have a rebleeding rate of 60% within 1- 2
      years. The presence of liver cancer and/or portal vein thrombosis has been associated with
      recurrent variceal bleeding. In a study of liver cancer patients in Hong Kong, 7.9% of
      patients developed at least 1 episode of variceal bleeding over the course of liver cancer.

      In patients with portal hypertension from cirrhosis, current guidelines recommend
      non-selective beta-blocker, endoscopic band ligation for esophageal varices after initial
      bleeding, and either cyanoacrylate injection for variceal obturation or transjugular
      intrahepatic portosystemic shunt for gastric varices after initial bleeding. However, it is
      unclear whether the above strategies will have the same clinical effect for patients with
      liver cancer and/or portal vein thrombosis who are at high risk for recurrent bleeding.

      Recently, the technique of endoscopic ultrasound (EUS) guided cyanoacrylate (glue) injection
      for variceal obturation has been described. In a study of patients with gastric variceal
      bleeding, EUS guided glue injection and coiling was reported to achieve hemostasis in all
      patients and 96% of the gastric varices remained obliterated during the follow-up period. To
      date, there has been no dedicated study to evaluate the role of EUS guided glue injection for
      prevention of future bleeding in patients at high risk for recurrent variceal bleeding such
      as those with liver cancer or portal vein thrombosis.

      The investigators propose this study to evaluate the feasibility and safety of EUS guided
      glue injection for follow-up variceal treatment in patients at high risk for recurrent
      variceal bleeding, such as those with liver cancer and/or portal vein thrombosis.
    

Detailed description: 
      Gastroesophageal variceal bleeding is one of the major complications of cirrhosis and occurs
      at a rate of 5 to 15% per year. 50% of patients with cirrhosis develop variceal bleeding
      during their lifetime. Large varix size, presence of red wale signs on endoscopy, and
      decompensated cirrhosis are predictors of variceal hemorrhage. Current first-line management
      of acute variceal bleeding includes a combination of vasoactive drug, endoscopic therapy and
      antibiotic prophylaxis. Despite advances in the management of acute variceal bleeding, the
      6-week mortality remains significant at 15 - 20% per episode of variceal bleeding.

      In patients who survive the acute variceal bleeding episode but without secondary
      prophylaxis, the median rebleeding rate is about 60% within 1- 2 years of the index bleeding
      with a mortality of 33%. The presence of hepatocellular carcinoma (HCC) and/or portal vein
      thrombosis (PVT) have been associated with recurrent variceal bleeding and worse outcome. In
      a retrospective study of 2928 HCC patients in Hong Kong, 7.9% of the patients developed at
      least 1 episode of variceal bleeding over the course of HCC. In cirrhotic patients with PVT
      but without HCC, variceal bleeding is not an uncommon complication.

      In patients with portal hypertension from cirrhosis, current guidelines recommend
      non-selective beta-blocker, endoscopic band ligation for esophageal varices after initial
      bleeding, and either cyanoacrylate injection for variceal obturation or transjugular
      intrahepatic portosystemic shunt for gastric varices after initial bleeding. However, it is
      unclear whether the above strategies will have the same clinical effect for patients with
      liver cancer and/or portal vein thrombosis who are at high risk for recurrent bleeding.

      Recently, the technique of endoscopic ultrasound (EUS) guided cyanoacrylate (glue) injection
      for variceal obturation has been described. In a study of patients with gastric variceal
      bleeding, EUS guided glue injection and coiling was reported to achieve hemostasis in all
      patients and 96% of the gastric varices remained obliterated during the follow-up period. To
      date, there has been no dedicated study to evaluate the role of EUS guided glue injection for
      prevention of future bleeding in patients at high risk for recurrent variceal bleeding such
      as those with liver cancer or portal vein thrombosis.

      The investigators propose this study to evaluate the feasibility and safety of EUS guided
      glue injection for follow-up variceal treatment in patients at high risk for recurrent
      variceal bleeding, such as those with liver cancer and/or portal vein thrombosis.
    

Intervention name(s): EUS-guided glue injection
Intervention type(s): Procedure
Intervention description(s): Experimental: EUS-guided glue injection Gastroesophageal varices > 3mm in diameter will be treated with EUS guided cyanoacrylate injection for variceal obturation in standard fashion. A conventional 19G needle (19G-Echotip needle, Cook Medical, USA) will be advanced into the target varix under real-time EUS guidance. Cyanoacrylate injection (Histoacryl, B. Braun Surgical, Germany) will be performed according to established protocol. Each aliquot of cyanoacrylate injection will consist of 0.5ml of Histoacryl + 0.7ml of lipiodol. 1 - 3 aliquots of cyanoacrylate injection may be given depending on the number of varices needed to be treated. EUS with colour Doppler will be used to monitor obliteration of blood flow in varices during and after cyanoacrylate injection.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Comparison of clinical outcomes of a prospective study cohort to those in a historical control group
Masking: None (Open Label)
Primary purpose: Prevention