1.1. Background and Aims: Ectopic embolization is the most serious complication of gastric variceal Cyanoacrylate injection for the treatment of isolated gastric varices (IGV) with gastro-renal shunt (GRS). To evaluate the safety and efficacy of modified balloon-occluded retrograde transvenous obliteration-assisted endoscopic Cyanoacrylate injection (E-BRTO) for the treatment of IGV with GRS.
1.2. Methods: Patients that had IGV with significant GRS, treated with E-BRTO, were included in this study. The GRS was temporarily occluded with an occlusion balloon and the IGV was treated by endoscopic Cyanoacrylate injection using the “sandwich technique”. Intra- and postoperative complications as well as the IGV eradication, re-bleeding, and recurrence rates were recorded and analyzed.
1.3. Results: 22 patients were included in this study. The mean volume of Cyanoacrylate used was 16.57±11.76mL. No deaths or serious complications were observed, including ectopic embolism and the worsening of hepatic and renal functions. IGV were eradicated in 22 cases (100%). Abdominal pain and fever was observed in one patient (4.55%), recurrence and re-bleeding of IGV in one patient (4.55%), who was recovery by another Cyanoacrylate injection.
1.4. Conclusions: E-BRTO is technically feasible, safe, and effective for the treatment of IGV associated with GRS in cirrhotic patients and worthy of clinical application.
Keywords:BRTO; Ectopic embolism; Gastro-renal shunt; Cyanoacrylate; Isolated gastric varices
2. IntroductionEsophagogastric varices are some of the most frequent complications of liver cirrhosis and portal hypertension. The incidence rate of isolated gastric varices (IGV) is lower than esophageal varices (EV). The prevalence of IGV in patients with portal hypertension is about 10%~50%. The frequency of bleeding is up to 10-36% and the re-bleeding rate ranges from 34% to 89%, but the mortality risk is as high as 25 ~ 55% [1, 2]. The current therapeutic options for IGV include medications, endoscopic therapy, surgery, and radiological interventions such as transjugular intrahepatic portosystemic shunt (TIPS) and balloon-occluded retrograde transvenous obliteration (BRTO) [3]. TIPS is useful for the treatment of IGV with large-diameter gastro-renal shunts (GRS). Some studies have shown that the long-term re-bleeding rate of IGV after TIPS is lower than that of tissue adhesive injection, but the incidence of hepatic encephalopathy is significantly higher [4].
3. Materials and MethodsIn this retrospective study, the data for patients that had IGV with or without EV and GRS and underwent E-BRTO between January 2016 and July 2019 at our center was collected. All patients provided informed consent prior to the treatment. The study was approved by the Institutional Review Board of the Fifth Medical Center of PLA General Hospital in Beijing. Upper gastrointestinal endoscopy was performed to assess the severity of IGV. Contrast-enhanced computed tomography and venography (CTV) of the portal venous system was performed to visualize the feeding and draining veins of the IGV (Figure 2A).
3.1. Inclusion criteria (1) Age between 20 and 75 years. (2) Presence of liver cirrhosis diagnosed by clinical examination or radiological imaging. (3) History of gastrointestinal bleeding on or before admission treated pharmacologically. 4) IGV diagnosed by endoscopy with no other potential source of bleeding. (5) A large GRS (6 mm < GRS < 10 mm) associated with IGV detected on preoperative imaging.
3.2. Exclusion criteria (1) Presence of hepatocellular carcinoma or other malignancies. (2) Past history of TIPS, surgical or endoscopic therapy for esophagogastric variceal bleeding. (3) Presence of large GRS too wide to be occluded by the largest available occlusion catheter. (4) Presence of hepatic encephalopathy, and (5) Uncontrolled infection.
3.3. Equipment The Olympus GIFQ260J endoscope (Olympus Optical, Tokyo, Japan), Cyanoacrylate (N-butyl-cyanoacrylate) (Compont, Beijing, China), DSA angiography machine (SIEMENS, AXIOM Artis U), balloon catheter (Termao, Japan), and a 23-G disposable injection needle (MTW, Germany) were used.
3.4. Technique A 5.5F balloon occlusive catheter was introduced into the hepatic vein through the right internal jugular vein or the right femoral vein. The wedge pressure of the hepatic vein was measured after balloon occlusion of the hepatic vein. The free pressure of the hepatic vein and the inferior vena cava pressure were measured after removal of the occlusion. Finally, the hepatic vein pressure gradient (HVPG) was calculated. Angiography was performed to visualize the prominent GRS and IGV (Figure 1A). According to the diameter of GRS, a balloon catheter with appropriate size was selected to block the GRS. The balloon occlusive catheter was introduced into the shunt and inflated to occlude the GRS (Figure 1B). Repeat angiography was performed to evaluate the position and size of the IGV (Figure 1C). The patient was placed in a left lateral position and the vital parameters of the patient (including heart rate, respiratory rate, oxygen saturation, and blood pressure) and electrocardiogram were continuously monitored preoperatively. Endoscopic examination was conducted to confirm the presence of GV and the volume of the varices (Figure 3A). Cyanoacrylate was injected into the GV at multiple points. Each injection was performed with the "sandwich technique" i.e. 1.5 mL Cyanoacrylate was sandwiched between two doses of 2 mL 50% glucose solution depending on the volume of the needle (Figure 3B). After each injection location, a satisfactory result was defined as hardening of the varices on gentle probing of the varices using a needle catheter. At the end of the procedure, before removing the balloon catheter, a repeat angiogram was performed to confirm the resolution of the IGV (Figure 1D). The therapy was defined as successful if the blood supply of the IGV was completely obliterated. The balloon occlusive catheter was then deflated and removed.
3.5. Treatment and follow-up Antibiotics were routinely administered for 5-7 days after the procedure [17]. Post-treatment repeat radiological imaging was conducted to observe the varices if any remained (Figure 2B). Re-examination by endoscopy was also performed to confirm the resolution of the IGV (Figure 3C and 3D), indicating successful treatment. A detailed operative note for each patient was carefully recorded. Repeat endoscopic examinations and follow-ups were performed after the E-BRTO procedure to identify complications, residual varices, recurrence, re-bleeding, aggravation of EV, and survival rates.
3.6. Statistical Analysis Statistical analyses were performed with SPSS 23.0. Continuous variables were presented as mean ± SD, while categorical variables were presented as the percentage ratio. P values < 0.05 were considered to be statistically significant.
4. ResultsTwenty-tow patients were included in this study, comprising 14 men and 8 women. The etiologies of cirrhosis were hepatitis B virus infection in 12 cases (54.54%), hepatitis C virus infection in two cases (9.09%), alcohol in four cases (18.18%), autoimmune-related in three cases (13.64%), and cryptogenic in one case (4.55%). All of the patients had IGV. All patients completed the E-BRTO procedure with a technical success rate of 100% (Table 1). The Child-Pugh scores for all of the 22 patients did not change after the treatment. The mean HVPG value was 14.25±2.41 mmHg. The mean volume of Cyanoacrylate used was 16.57±11.76 mL, and the mean number of puncture sites was 5.28±4.0. Postoperative complications included fever (1 of 22, 4.55%) and abdominal pain (1 of 22, 4.55%). All complications were transient and resolved within 24 h with symptomatic therapy.
5. DiscussionIn contrast to EV, the anatomy and hemodynamic indexes of IGV are more complex [3]. Bleeding from IGV is usually large in volume and the mortality rate is high [1]. Although BRTO has been shown to have good clinical outcomes in IGV treatment, the optimal treatment for IGV has not yet been established.18 Endoscopic Cyanoacrylate injection has recently become the first-line therapy for IGV [19]. A potentially fatal complication of Cyanoacrylate injection is the development of ectopic embolism due to migration of the Cyanoacrylate into the systemic circulation [20]. A multicenter study showed that the incidence of asymptomatic ectopic embolism after cyanoacrylate injection therapy is high [21]. In particular, the risk of ectopic embolism in IGV accompanied by GRS is significantly high [14]. Therefore, the existence of GRS is an important factor in the selection of treatment methods for IGV. Kanagawa et al. first reported the use of BRTO in 1991 [22].Many years of clinical practice have demonstrated that BRTO is safe and effective for the treatment of IGV [23]. Modified BRTO can achieve better therapeutic effects than traditional BRTO and TIPS [24]. Hamamoto et al [25]. successfully treated a IGV patient with a combined technique, in which the sclerosant was endoscopically injected into the IGV while the GRS was temporarily occluded by BRTO. Studies have found that titanium clips can be safely used along with tissue adhesive injection in the treatment of IGV Table 1: Patient Characteristics
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Yan-Ling Wang. Safety and Efficacy of Modified BRTO-Assisted Endoscopic Cyanoacrylate Injection for the Treatment of Isolated Gastric Varices with Gastro-Renal Shunt. Annals of Clinical and Medical Case Reports 2020