Treatment of Gastric Varices Using EUS Guided Techniques
Condition: Gastric Varix
MeSH terms: Esophageal and Gastric Varices
Study type: Interventional

Summary: 
      Bleeding from gastric varices (GV) is associated with high mortality. Injection of
      cyanoacrylate (CYA) using standard gastroscopes has demonstrated higher hemostasis and lower
      rebleeding rates compared to band ligation or sclerotherapy. Nevertheless CYA treatment is
      known to be associated with significant adverse events. Pulmonary embolism due to CYA
      injection is a serious and sometimes fatal complication of this therapy. Romero-Garcia et al.
      recently showed that, even these patients usually have respiratory symptom, this complication
      can be present in asymptomatic patients and with only CT pathological images showing it. On
      the other hand, risk of glue embolism, has been described to be dependent on the volume of
      CYA injected, being significantly greater with high volume. Other complications related to
      CYA injection are, hemorrhage from post injection ulcers, fever, peritonitis, needle
      impaction, and even death. Also the injection material can cause serious damage to the
      endoscope.

      Currently endoscopic treatments are CYA injection under direct visualization using a standard
      gastroscope and treatment under EUS guidance with injection of CYA, coils or both. However,
      to date, it is unknown whether one of these techniques is technically more feasible or causes
      less adverse events than the other.

      Treatment under EUS guidance may improve results because of precise targeting of the varix
      lumen or afferent feeding veins. This allows the vein to be obstructed with a small amount of
      CYA, less than used for the "blind" injection of GV with standard endoscopic technique and
      may reduce the risk of glue embolism. EUS can confirm varix obliteration by using Doppler.
      Also visualization of GV by using EUS is not impaired by blood or food in the stomach and
      thus can be performed in the setting of active hemorrhage.
    

Detailed description: 
      Coils that are currently used for intravascular embolization treatments can be delivered
      under EUS guidance offering a new treatment approach. Romero-Castro et al. previously
      reported a case series by using up to 20 coils to eradicate gastric fundic varices (GFV) in 4
      patients, with a 75% success rate. More recently this author compared in a multicenter study
      the treatment of GFV using EUS guide injection of N-butyl cyanocryloate with Lipiodol vs. EUS
      guide injection of coils alone. Both techniques had excellent results with GFV obliteration
      rate of 94.7% and 90.9% respectively. However 47.4% of the patients in the CYA group required
      more than one session and 36.4% in the coil group either required additional coil or CYA
      placement. There was a significant difference in the overall adverse event rate between CYA
      group (57.9%) and coil group (9.1%), due to glue pulmonary embolism.

      Coils in conjunction with CYA injection may reduce or eliminate the risk of glue
      embolization. Coils with attached synthetic fibers ("wool coils") may function as a scaffold
      to retain CYA within the varix and may decrease the amount of glue injection needed to
      achieve obliteration. Binmoeller et al. described them 6 years experience in 152 patients
      with GFV treated with 2-octyl cyanocrylate plus coils. Patients had active hemorrhage (5%),
      recent bleeding (69%) or were treated for primary prophylaxis (26%). Treatment was
      technically successful in 151 patients (>99%), with mean number of coils of 1.4 and mean
      volume of CYA of 2 ml. Follow-up was possible in 125/151 patients (100 using EUS examinations
      and 25 with clinical and/or EGD follow-up). Complete obliteration was confirmed with
      EUS-Doppler image in 93/100 (93%). Post-treatment bleeding occurred in 20 of 125 patients
      (16%) and only 10 (50%) where GFV related bleeding. Mild post procedure abdominal pain
      occurred in 4 of 125 patients (3%), and clinical signs of pulmonary embolization were seen in
      1 patient (1%). Another 4 of 125 patients (3%) presented with minor delayed upper GI bleeding
      from coil/glue extrusion.

      The aim of this study is to describe and compared efficacy and safety two different EUS
      guided techniques for GFV treatment (Coils + CYA vs. Coils alone). Efficacy will be measure
      by technical success defined as successful technique performance and functional success
      defined as complete obliteration of the varix and absence of Doppler flow on EUS. Safety will
      be determinated by measure of adverse events related to the procedure or gastric varices
      within and after 30 days of the procedure.

      METHODS Setting: Instituto Ecuatoriano de Enfermedades Digestivas (IECED), OmniHospital
      Academic Tertiary Center. Patients will be included from March 2016 to June 2017. The study
      protocol and consent form has been approved by the Institutional Review Board and will be
      conducted according to the declaration of Helsinki. Patients will sign an informed consent.

      All procedures will be performed in a hospital-based interventional endoscopy suite, where
      fluoroscopy is available, by one endoscopist (C.R.M). Procedures will be performed under
      general anesthesia and under antibiotics prophylactic. After the procedure, patients will be
      observed for 2 hours in the recovery room before being discharged. Follow up will be
      performed by standard endoscopy and EUS at 3 and 6 months post procedure. Hemostasis, early
      post treatment bleeding and late post treatment bleeding will be considered according Baveno
      VI concensus. Complete obliteration of the varix will be defined as absence of Doppler flow
      on EUS.

      EUS will be performed using a 3.8 mm working channel linear-array therapeutic echoendoscopes
      (EG 3870UTK; Pentax, Hamburg, Germany), attached to an US console (Avius Hitachi, Tokyo,
      Japan). Active flow within GFV will be confirmed by color Doppler before and after therapy.

      Endoscopic Procedure: First a standard diagnostic upper endoscopy will be performed in order
      to classify the varices according to the classification of Sarin and Kumar. As mentioned
      before only GOV II and IGV I varices will be included. Once the patient is conceder a
      candidate will be randomized to be treated with Coils plus CYA (Group A) or only Coils (Group
      B). Then the echoendoscope will be positioned in the distal esophagus (anterograde
      trans-esophageal, transcrural approach) or in the gastric fundus (trans-gastric approach) to
      visualize the gastric fundus, intramural varices and feeder vessels. The trans-esophageal
      approach will be preferred between both approaches. Once positioned, water will be instilled
      in order to fill the gastric fundus, improved acoustic coupling and visualization of GFV. EUS
      color Doppler imaging will be used to allow direct visualization of the varices flow. Then a
      19G EUS-FNA needle (Expect flexible; Boston Scientific, USA) will be used to puncture the
      vessel, the stylet will be withdrawn and a syringe with negative pressure will be used to
      evaluate blood return and therefore intravascular location. After this 1 ml of saline
      solution will be instilled to prevent blood clotting in the needle light and then 2 ml of
      water-soluble contrast (Ultravist, Bayer, Ecuador), under fluoroscopy evaluation, will be
      used in order to ensure intravascular location and varix flow direction (afferent or
      efferent). If the patient is on Group A coils and then 2-Octyl-CYA will be injected, and if
      it is on group B only coils will be injected into the varix. The coils used will be
      intravascular embolization coils (10-16 mm coiled diameter, 12-20 cm straight lengths, 0.035
      inches in diameter, Nester Embolization Coil; Cook Medical) and will be delivered into the
      vessel through the FNA needle using a 0.035-inch hydrophilic guidewire as a pusher. Special
      attention will be paid to not place the needle tip at the counter wall because of the risk of
      perforation, bleed, coils extrusion and to allow enough space for the coil to curl. The
      2-Octyl-CYA (Dermabond; Ethicon, Piscataway, NJ) will be injected using the same needle and
      then 1 mL of normal saline solution to flush the glue completely through the catheter. The
      diameter and number of coils (10 to 16 mm) and the volume of 2-Octyl-CYA injected will be
      calculated according to the diameter of the vessel measured on EUS. After 15 to 30 seconds
      once the CYA is solidified and the risk of bleeding by puncturing decreases, the needle will
      be withdrawn. Finally obliteration of the vessel will be evaluated using Doppler imaging 5
      minutes later.

      The 2-octyl-CYA compared to the N-butyl-CYA, for the treatment of GV, has demonstrated
      similar efficacy for hemostasis and prevention of recurrent bleeding. It has a longer
      polymerization time, thus it does not need to be diluted with Lipiodol (which is viscous and
      makes injection more difficult). Also allows a longer injection time and reduced risk of
      damage to the endoscope by glue impaction of the working channel. Lipiodol enable
      fluoroscopic visualization of the injected vessel and confirmation that the feeder vessel had
      been accurately targeted. Also it is useful to identify an asymptomatic pulmonary embolism on
      an X-ray. However it can be replaced with water-soluble contrast to evaluate the varix. On
      the other hand glue embolization has only been reported immediately after injection, so if
      there are any suspicion of embolism because a high dose injected of CYA, in a asymptomatic
      patient, a CT can be performed in order to confirm it.

      Statistical analysis: Baseline characteristics will be compared between the two group using
      Chi-square o Fisher Test for categorical variable, and for continuing variables, we will use
      the Mann-Whitney Test. Diagnosis efficacy will be measured thought sensitive, specificity and
      accuracy. All the statistical analysis will be performed using SPSS software suite v.22.

      Limitations: It is a simple blind study, performed in a single center by one endoscopist
    

Intervention name(s): EUS-guided injection of coils with cyanoacrylate; EUS-guided injection of coils
Intervention type(s): Procedure; Procedure
Intervention description(s): First a standard diagnostic upper endoscopy will be performed in order to classify the varices according to the classification of Sarin and Kumar. Only GOV II and IGV I varices will be included. Once the patient is conceder a candidate will be treated with Coils plus CYA (Group A); First a standard diagnostic upper endoscopy will be performed in order to classify the varices according to the classification of Sarin and Kumar. Only GOV II and IGV I varices will be included. Once the patient is conceder a candidate will be treated with only coils (Group B).
Other intervention name(s): Drug: cyanoacrilate; Device: coils; Device: coils
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: EUS, cyanoacrylate, coils, gastric varices