Gastric varices are present in 5% 30% of patients with ENDOSCOPY CORNER

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8: ENDOSCOPY CORNER Low Incidence of Complications From Endoscopic Gastric Variceal Obturation With Butyl Cyanoacrylate LIU FANG CHENG,* ZHI QIANG WANG,* CHANG ZHENG LI,* WU LIN, ANTHONY E. T. YEO, and BO JIN *Department of Gastroenterology and Hepatology, Chinese People=s Liberation Army General Hospital, Beijing, China; Department of Digestive Diseases, Shijitan Hospital, Beijing, China; Sherman Oaks, California; and Department of Digestive Diseases, Naval General Hospital, Beijing, China BACKGROUND & AIMS: Endoscopic variceal obturation with tissue adhesive is used to control gastric variceal bleeding. We investigated the prevalence of serious complications from this therapy. METHODS: We performed a retrospective analysis of complications that occurred in 753 patients with gastric variceal hemorrhages who were hospitalized in 2 tertiary referral hospitals. All patients received N-butyl-2-cyanoacrylate as therapy for endoscopic variceal obturation. RESULTS: Complications occurred in 51 patients. Thirty-three patients experienced rebleeding because of early-onset (within 3 months) extrusion of the N-butyl-2-cyanoacrylate glue cast (4.4%), 10 patients developed sepsis (1.3%), and 5 patients developed distant embolisms (0.7%; 1 pulmonary, 1 brain, and 3 splenic). One patient had major gastric variceal bleeding after endoscopic variceal obturation (0.1%), 1 developed a large gastric ulcer (0.1%), and 1 had mesentery hematoma, hemoperitoneum, and infection in the abdominal cavity (0.1%). The complicationrelated mortality was 0.53% (3 deaths from sepsis and 1 death from rebleeding after early-onset glue cast extrusion). CON- CLUSIONS: The occurrence of complications after endoscopic variceal obturation with N-butyl-2-cyanoacrylate in gastric varices treatment is rare. Keywords: Gastric Variceal Obliteration; Histoacryl; Recurrent Variceal Bleeding; Ectopic Embolism. View this article s video abstract at Gastric varices are present in 5% 30% of patients with portal hypertension, and the overall incidence of bleeding caused by variceal rupture varies from 3% 30%. 1 3 Although gastric varices are less common than esophageal varices, gastric variceal bleeding is more severe and difficult to control. 4 Endoscopic variceal ligation (EVL) and endoscopic variceal sclerotherapy (EVS) have been reported to have high rates of control of gastric variceal bleeding, 1,4 7 but the major drawbacks are the high risk of rebleeding after EVS and the potential of partial ligation of large gastric varices by EVL, resulting in fatal bleeding. 1,8,9 Randomized controlled studies have demonstrated that endoscopic variceal obturation (EVO) of gastric varices with tissue adhesive was more effective than EVS or EVL, with a hemostatic rate of 87% 93%, a rebleeding rate of 22% 31%, and a mortality rate of 11% 29%, whereas in patients who underwent EVL or EVS, the corresponding rates were 45% 93%, 25% 54%, and 15% 48%, respectively. 1,5 Thus, EVO is preferred in management of gastric varices. 1,4,5,10 Unlike esophageal varices, gastric varices are located deeper in the submucosa. Sclerotherapy with or without ligation is usually unable to control gastric variceal bleeding, and in addition, such procedures might be hazardous. 11 Some studies have suggested that EVO was effective in stopping acute gastric variceal bleeding, 2,10,11 and this has emerged as the initial therapy of choice. 2 Although EVO is efficacious in stopping gastric variceal bleeding, serious and uncommon complications can still occur and are potentially lethal. In this study, a retrospective analysis of complications that occurred in a case series of 753 patients with gastric varices who underwent EVO therapy was conducted. Patients and Methods Patients The patient population consisted of 3346 consecutively admitted patients with episodes of variceal bleeding who received endoscopic therapy and were hospitalized in either the General Hospital of Chinese People s Liberation Army (GHCPLA) between January 1996 and April 2006 or Beijing Shijitan Hospital (BSH) between March 2003 and December This study population was divided into 2 groups, a cohort comprising 2953 cases with esophageal variceal bleeding who received either EVL or EVS and 753 patients with gastric variceal hemorrhage who received EVO therapy. The latter group constituted the study cohort (n 753). At BSH, EVO therapy was conducted by a consultant endoscopist from GHCPLA. The mean age of the study cohort was 51 years (95% confidence interval [CI], 49 51). Most patients were male (72.6%), and the most common cause of gastric varices was hepatitis B related cirrhosis (69.2%) (Table 1). Gastric varices were classified according to the description of Sarin et al. 3 Besides the classic gastroesophageal varices (GOV) 1 and GOV2, there were some cases with GOV Abbreviations used in this paper: BSH, Beijing Shijitan Hospital; CI, confidence interval; CT, computed tomography; EVL, endoscopic variceal ligation; EVO, endoscopic variceal obturation; EVS, endoscopic variceal sclerotherapy; GHCPLA, General Hospital of Chinese People s Liberation Army; GOV, gastroesophageal varices; IGV, isolated gastric varices; TIPS, transjugular intrahepatic portosystemic shunt by the AGA Institute /$36.00 doi: /j.cgh

2 September 2010 EVO THERAPY COMPLICATIONS FOR GASTRIC VARICES 761 Table 1. Clinical Features of Patients With Gastric Varices Clinical features No. of patients Percentage Male Female Classification of gastric varices GOV GOV GOV IGV IGV2 0 0 Child Pugh classification A/B/C/not classified 244/297/179/ /39.4/23.8/4.4 Etiology of gastric varices Cirrhosis Viral hepatitis B Viral hepatitis C Viral hepatitis B C Viral hepatitis B alcoholism Alcoholism Immunopathologic (AIH or PBC) Cryptogenic Cavernous transformation of portal vein Portal vein malformation Cryptogenic portal hypertension Pancreatic carcinoma Pancreatic trauma Associated with hepatocellular carcinoma AIH, autoimmune hepatitis; PBC, primary biliary cirrhosis. who had varices extending from esophagus toward both the lesser curve and the fundus of the stomach that could not be attributed to either GOV1 or GOV2. This type of GOV was referred to as GOV1-2. EVO Therapy With N-Butyl-2-Cyanoacrylate In this series of 753 patients, a total of 783 sessions of EVO therapy with N-butyl-2-cyanoacrylate were performed. Emergency treatments were given in 156 sessions, with the remaining 627 treatments performed electively. All the patients signed an informed consent form before undergoing endoscopy. The protocol was approved by the local institutional ethics committees. All 156 emergent treated patients had gastric variceal bleeding during 24 hours before the procedure. During EVO therapy it was observed that blood clot was attached on the varices, fresh red thrombus was located in the varices, or active bleeding was detected with bloody fluid accumulation in gastric cavity. When a patient was actively bleeding or when a substantial accumulation of blood and fluids occurred in gastric cavity, it was difficult to detect the hemorrhagic varices, especially for those with isolated gastric varices (IGV) 1. In which case, changing the position of the patient from left lateral recumbent side onto his right side was helpful to unveil the location of the fundal varices. All detected varices should be obliterated in a single or consecutive sessions of endoscopic procedure. In cases of GOV1-2, the gastric varices that were located on both the lesser curve and the fundus were completely obliterated with EVO therapy. In patients with GOV and esophageal varices, the latter were also obliterated with EVL or EVS. An oblique viewing fiber (GIF-K10, GIF-K20; Olympus Optical Co Ltd, Tokyo, Japan) or video endoscope (EG-450G; Fujinon Corporation, Saitama, Japan) or a forward viewing endoscope (EG-410HR; Fujinon Corporation) was used in treatment. After the gastric varices were detected and localized under gastric endoscopy, a disposable endoscopic injector with 23- gauge needle (Interject Sclerotherapy Needles; Boston Scientific, Boston, MA) was used via the accessory channel. Several 2-mL sterile syringes were used for preparation of glue mixture premixed with N-butyl-2-cyanoacrylate (Histoacryl blue; B. Braun Melsungen AG, Melsungen, Germany) and Lipiodol (Guerbet Laboratories, Aulnay-sous-Bois, France) at a ratio of 1:1 (v/v). Each syringe was loaded with 2 ml of glue mixture. During the early years of the study, the sandwich injection method was used in 419 sessions at both institutions. 12 Briefly, the endoscopic injector was filled with 1.0 ml of Lipiodol, and immediately after gastric varix puncture, the glue mixture was injected into the varices followed by another 1.0 ml of Lipiodol flush. After October 2003, a modified sandwich injection model was adopted, with another 364 sessions in which the endoscopic injector was prefilled with sterile saline. After puncture of the gastric varix, 0.3 ml of Lipiodol was injected followed by glue mixture, and another 0.3 ml of Lipiodol and 1.2 ml of saline were used to flush the injector. The amount of glue mixture used for each EVO session was based on the type of varices and the experience of the endoscopist. For patients with IGV, the usual amount was 3 5 ml; for patients with GOV, 1 2 ml; and in the current cohort, patients with GOV or IGV1, the amount of glue mixture injected was ml (mean standard deviation, ml) and ml ( ml), respectively. After each EVO treatment, 5 ml of blood sample was obtained from the patient and cultured if he/she showed signs of infection. Patients who showed signs of infection received antibiotic regimen before or after EVO therapy. Patient Follow-up All the patients were followed up endoscopically at 1, 3, and 6 months after initial EVO therapy. After 6 months, the follow-up was scheduled yearly until June 2008 or until death of the patient. When complications occurred, the patient was readmitted to the hospital for examination and treatment as required. Statistical Analysis Data were expressed as mean standard deviation or 95% CI. Pearson 2 test was used to evaluate the difference in occurrence rates among distinct groups by Stata 7.0 software (Stata Corporation, College Station, TX). A P value of.05 was statistically significant. Results Follow-up A total of 49 patients (49 of 753, 6.5%) died, and 68 patients were lost during follow-up. The causes of death were 14 cases from liver failure, 14 from uncontrolled upper gastrointestinal bleeding, 11 from liver cancer, 3 from infection and sepsis, 2 from renal failure, and the remaining 5 from other

3 762 CHENG ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 9 diseases not related to portal hypertension. The survival analysis has been reported elsewhere. 12 Rebleeding Due to Early-Onset Extrusion of N-Butyl-2-Cyanoacrylate Cast Glue cast extrusion usually began 1 month after treatment and rarely occurred after the first year. 12 Most of the glue cast extrusion occurs during 3 months after injection. 13 The rebleeding cases that occurred within 90 days after treatment were carefully examined endoscopically, and extrusion of N-butyl-2-cyanoacrylate cast was validated. Hemorrhage that occurred 90 days after EVO therapy with detection of glue cast extrusion was defined as rebleeding as a result of early-onset extrusion of N-butyl-2-cyanoacrylate cast, although the presence of cyanoacrylate casts did not exclude that rebleeding caused by other varices. Thirty-three patients (4.4%) experienced rebleeding caused by early-onset glue cast extrusion, and one of them died. The types of varices of these rebleeding patients constituted 13 cases of GOV1, 10 cases of GOV2, 7 cases of GOV1-2, and 3 cases of IGV1. The mean time to rebleeding occurred at 23 days (95% CI, 15 30) after EVO therapy. Initially, small-dosage injections (1 2 ml) over several sessions were used. However, a 28-year-old male patient who experienced 5 episodes of rebleeding after 2 ml of glue mixture injection at the initial treatment had an emergency transjugular intrahepatic portosystemic shunt (TIPS) procedure. Angiography demonstrated incomplete obturation of the gastric varices, and the contrast medium leaked from the glue cast extrusion foci into the gastric lumen. After this case, the obturation procedure was altered by obliterating the varices as completely as possible at the initial session. Distant Embolization Distant embolism was defined as embolic symptoms occurring 3 days after treatment along with radiopaque spots detected by x-ray or computed tomography (CT) scanning. Distant embolism occurred in 5 cases (0.7%), and all of them received sandwich injection EVO. By contrast, no embolism occurred in those with modified sandwich injection (P.037). The volumes of glue mixture injected in these 5 embolic cases were 3 ml, 2 ml, 2 ml, 2 ml, and 2 ml, respectively. Because no systematic screening for distant embolism was conducted, some patients with asymptomatic embolism might have been missed. Among these 5 embolic cases, 1 patient with GOV1-2 had a pulmonary embolism. Another patient with GOV1-2 suffered a brain embolism that resulted in hemiplegia of the right side of his body; he recovered in 5 days. CT scan of the brain detected deposition of radiopaque in the left frontal lobe of the brain (Figure 1A). Spleen embolisms identified in the remaining 3 cases consisted of 1 case of GOV1, 1 case of GOV1-2, and 1 case of IGV1. CT scans detected deposition of radiopaque droplets in the spleen (Figure 1B). All 3 patients with splenic embolism recovered well. There was no mortality directly related with embolism. Sepsis There were 10 patients who had fevers, chills, and elevated white blood cell counts with positive blood cultures. The follow-up for these 10 septic patients ranged from 2 60 months ( months). Infections occurred days after treatment ( days). The most common pathogens identified were Escherichia coli and Pseudomonas aeruginosa Figure 1. Embolization associated sandwich injection EVO procedures. (A) Brain embolism after EVO by CT scan; frontal lobe of the left brain (black arrow). (B) Splenic embolism by abdominal CT scan showed scattered radiopaque droplets in the spleen (white arrows). (Table 2). Six patients underwent emergency EVO therapy and received blood transfusion before EVO treatment. The remaining 4 patients underwent elective EVO treatment. The occurrence rate of sepsis in patients who underwent emergency or elective EVO therapy was 3.85% and 0.64%, respectively (Table 2) (P.001). Infections occurred as early as 3 days after EVO injection (3 patients) to as late as 150 days after the therapy. In these late-onset infected patients ( days, 7 patients), pus was detected on the extruded glue cast (Figure 2), suggestive that this was the origin of infection. Three deaths occurred at days 30, 40, and 50 after the procedure among the 10 septic patients.

4 September 2010 EVO THERAPY COMPLICATIONS FOR GASTRIC VARICES 763 Table 2. Occurrence of Sepsis After EVO Therapy Bacterium growing in blood culture Onset after EVO therapy (d) No. of Injections Injection amount of BC (ml) Site of injection Blood transfusion Child-Pugh classification EVO therapy Type of varices No. Gender Age (y) Diagnosis 1 Male 62 HBV-related cirrhosis IGV1 B Elective No Fundus Staphylococcus albus 2 Male 52 HCC GOV1-2 C Emergent Yes Fundus E coli 3 Male 31 HBV-related cirrhosis GOV1-2 C Emergent Yes Cardia E coli 4 Female 66 PBC GOV1 B Emergent Yes Fundus Streptococcus viridans 5 Female 47 HBV-related cirrhosis IGV1 C Emergent Yes Fundus Streptococcus haemolyticus 6 Female 45 HCV-related cirrhosis IGV1 B Elective No Fundus P aeruginosa 7 Female 47 HBV-related cirrhosis IGV1 B Emergent Yes Fundus P aeruginosa 8 Male 69 HBV-related cirrhosis IGV1 C Elective No Fundus P aeruginosa 9 Male 64 HBV-related cirrhosis IGV1 B Elective No Fundus E coli 10 Male 40 HBV-related cirrhosis IGV1 C Emergent Yes Fundus E coli BC, N-butyl-2-cyanoacrylate; HCC, hepatocellular carcinoma; PBC, primary biliary cirrhosis. Figure 2. Bacterial infection after extrusion of N-butyl-2-cyanoacrylate. Pus detected by gastric endoscopy on the extruded glue cast and at the extrusion foci. Massive Gastric Variceal Bleeding Massive bleeding occurred in 1 patient during EVO therapy. Defined as IGV1 endoscopically, the patient received elective EVO treatment. After the first bolus injection of N-butyl-2-cyanoacrylate, blood spurted out from the injection site as soon as the injector was withdrawn. Hemostasis was not achieved until the fourth consecutive bolus injection of N-butyl-2-cyanoacrylate. Giant Gastric Ulcer The patient with GOV1 received elective EVO treatment. After N-butyl-2-cyanoacrylate injection, the patient had severe upper abdominal pain. Analgesic was required during the subsequent 3 days. Endoscopy 2 weeks after treatment detected a giant ulcer in the gastric fundus, which healed in 14 months (Figure 3). Mesentery Hematoma and Hemoperitoneum With Infection in Abdominal Cavity This patient with IGV1 received the second session of EVO therapy as a result of rebleeding. After the treatment, he had high fever and complained of abdominal distention. Abdominal puncture showed bloody ascites, and culture identified P aeruginosa. He did not respond to medical treatment and was operated on. Surgery showed that he had developed a mesentery hematoma. He made an uneventful recovery. Complications Due to Early Polymerization of N-Butyl-2-Cyanoacrylate Accidental obliteration of endoscope accessory channel or injector occurred in 6 sandwich injection sessions and in 2 sessions with modified sandwich injection. Damage to the endoscope occasionally occurred at the air and water channel as a result of the channel being choked by solidified glue. This occurred 7 times between 2004 and 2006, and servicing was required 5 times. Other Mild Reactions Twenty cases had cough during the injection. No radiopacities were detected in the lung, pericardium, or dia-

5 764 CHENG ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 9 Figure 3. A giant gastric ulcer formed after submucous injection of tissue adhesive. (A) During glue injection. (B, C) One month after injection, a giant ulcer was found with a white-yellowish base and scattered submucous hemorrhage foci, with congestion and edema of the surrounding mucosa. (D) Five months after injection, the ulcer showed a clear boundary, with white-yellowish base and fresh granulation. (E) Eight months after injection, the ulcer displayed a clear base and more granulation. (F) Fourteen months after injection, the ulcer was almost healed. phragm after treatment (data not shown). Another 12 patients complained of upper abdominal pain, and these symptoms disappeared within hours. A few cases complained of heartburn, and this too disappeared in hours. Serious complications as a whole occurred in 51 patients in this cohort of 753 cases with the morbidity of 6.77%, and 4 of them died, which accounted for a mortality of 0.53%. Discussion The use of N-butyl-2-cyanoacrylate for gastric varices treatment was first introduced in Despite its efficacy, EVO with cyanoacrylate can create complications 4 including early polymerization leading to needle adhesion to the varices, embolization, bacteremia, esophageal perforation, peritoneal cavity extravasation, and splenic infarction. 4,15 17 Thromboembolism is a primary complication of EVO with tissue glue. All 5 embolic cases occurred with sandwich injection. The volume of Lipiodol used to flush the injector in sandwich injection was 1 ml, compared with 0.3 ml in modified sandwich method. Lipiodol was used as a diluent of N-butyl-2-cyanoacrylate to prevent early polymerization. 18 The application of higher volume of Lipiodol before glue injection might prevent early exposure of N-butyl-2-cyanoacrylate to blood and delay glue clogging and increase the risk of glue migration and embolization. The usage of higher volume of Lipiodol after glue injection might also dilute the glue mixture that has not polymerized and increase risk of distant embolization. In modified sandwich injection, smaller volumes of Lipiodol were used before and after glue injection. This reduced the risk of embolization. Drainage of gastric varices via a gastrorenal shunt occurred in 85% of cases, via a gastrophrenic shunt in 10% of cases, and via a gastropericardiophrenic shunt in 5% of cases. 19 Lumps of polymerized N-butyl-2-cyanoacrylate can flow through from these shunts into vessels, resulting in distant embolisms. Bacteremia or sepsis is another significant complication after EVO therapy. 15,20 In this study, septic morbidity in emergency procedures (3.85%) was significantly higher than that in elective treatment (0.64%). Considering the high rate of bacteremia in active variceal hemorrhaging patients ranging from 1.9% 11%, 21 bacteremia present before the procedure cannot be ruled out. Because febrile symptoms were not reported in the 6 patients

6 September 2010 EVO THERAPY COMPLICATIONS FOR GASTRIC VARICES 765 before EVO procedure, preexisting bacteremia is unlikely. The fistula due to intraluminal extrusion of N-butyl-2-cyanoacrylate cast connects the gastric lumen and the blood vessel, thereby facilitating bacterial invasion. As described above, pus was detected on the extruded glue cast, indicating infection. Unlike other reports, 15 the most commonly detected bacteria were E coli and P aeruginosa. All 6 septic patients with emergency treatment had blood transfusions, which were recognized as one of the risk factors of bacteremia. 15 Prophylactic antibiotics for patients undergoing emergent cyanoacrylate injection were recommended. 20 The rebleeding rate after EVO treatment was 12.5% 52% after 1 year, 22 with more than half occurring during the first month after treatment. 23 Injected N-butyl-2-cyanoacrylate can embolize the vessel and result in an inflammatory response followed by a chronic granulomatous reaction and fibrosis. 24 The glue cast extrudes through recanalization of previously embolized vessels. 24 If variceal obturation is incomplete, rebleeding can occur. If the glue cast sloughs out early, fibrosis of the obturated varices would be immature, and rebleeding would happen after cast extrusion. The complete obliteration of the varices can reduce the rebleeding rate and can be assessed by careful palpation by using the injector after injection. This can also be judged by the observation that only drops of glue and blood effused from the injection site after retraction of the injector from the varix. Epigastric CT scanning 3 5 days after the procedure was also helpful to evaluate the efficacy of the obturation. When the mixture of N-butyl-2-cyanoacrylate and Lipiodol was extravascularly injected into gastric mucosa, polymerization products were oval-shaped with irregular margins. These submucous glue polymers can result in caseous necrosis. 25 Because the stomach wall abounds with vessels, inflammation would be more severe and prolonged. Thus, the occurrence of gastric ulceration might attribute to extravascular injection. This toxicity might be due to the cyanil radical or the formaldehyde released during cyanoacrylate biodegradation. 26 Hemoperitoneum has been reported in patients undergoing percutaneous preoperative portal vein embolization with N-butyl-2-cyanoacrylate. 27 One patient in this series experienced mesentery hematoma and hemoperitoneum with bacterial infection after EVO therapy. Because P aeruginosa infection is usually iatrogenic, this infection is likely to be EVO-related. Seewald et al 18 suggested a multi-injection method with 1 ml of glue mixture for each injection. However, 1 patient experienced massive bleeding with only 1 bolus injection of 2 ml. It appears essential to estimate the required glue mixture dosage before injection by an experienced endoscopist. If a large varix is present, a large dosage should be delivered in the first injection. The injection should be quick enough to prevent the glue solidification in the injector or the needle sticking in the varix. Accidental endoscope damage is occasionally associated with EVO therapy with N-butyl-2-cyanoacrylate. This kind of endoscopic damage is usually due to gluing of the air and water channel, most commonly caused by the operator. Prefilling with Lipiodol in the accessory channel might prevent gluing of the endoscopic channel. It was also essential to keep the endoscope 2 3 cm away from the targeted varices to prevent the endoscope from contacting the injected glue. After injection of the glue, suction usage was avoided for 20 seconds to prevent entry of the unpolymerized glue into the endoscope. Once the endoscope channel was glued, air insufflation and water effusion would be difficult or impossible to achieve. If a lump of glue was attached to the end of the endoscope, it could be gently removed by using an injection needle. If the air and water channel was completely glued, the scope was sent to a technical service center, which replaced the air and water nozzle. This study has potential limitations. First, this is a retrospective study with inherent limitations such as selection bias. However, recall bias was substantially reduced because all the data were recorded immediately after individual treatment. Second, the distribution of the patients among sandwich injection and modified sandwich injection groups was not randomized as a result of ethical considerations. In summary, the occurrence of complications after EVO therapy with N-butyl-2-cyanoacrylate in gastric varices treatment was uncommon. The complication-related mortality was found to be 0.53%. Prima facie, the modified sandwich injection method with less Lipiodol usage appears to significantly reduce the occurrence of EVO-related complications. Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at and at doi: / j.cgh References 1. Toubia N, Sanyal AJ. 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7 766 CHENG ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No Soehendra N, Grimm H, Nam VC, et al. N-butyl-2-cyanoac rylate: a supplement to endoscopic sclerotherapy. Endoscopy 1987;19: Chen WC, Hou MC, Lin HC, et al. Bacteremia after endoscopic injection of N-butyl-2-cyanoacrylate for gastric variceal bleeding. Gastrointest Endosc 2001;54: Hwang SS, Kim HH, Park SH, et al. N-butyl-2-cyanoacrylate pulmonary embolism after endoscopic injection sclerotherapy for gastric variceal bleeding. J Comput Assist Tomogr 2001; 25: Cheng PN, Sheu BS, Chen CY, et al. Splenic infarction after histoacryl injection for bleeding gastric varices. Gastrointest Endosc 1998;48: Seewald S, Ang TL, Imazu H, et al. A standardized injection technique and regimen ensures success and safety of N-butyl-2- cyanoacrylate injection for the treatment of gastric fundal varices (with videos). Gastrointest Endosc 2008;68: Hong CH, Kim HJ, Park JH, et al. Treatment of patients with gastric variceal hemorrhage: endoscopic N-butyl-2-cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol 2009;24: Rerknimitr R, Chanyaswad J, Kongkam P, et al. Risk of bacteremia in bleeding and nonbleeding gastric varices after endoscopic injection of cyanoacrylate. Endoscopy 2008;40: Low DE, Shoenut JP, Kennedy JK, et al. Infectious complications of endoscopic injection sclerotherapy. Arch Intern Med 1986; 146: Caldwell SH, Hespenheide EE, Greenwald BD, et al. Enbucrilate for gastric varices: extended experience in 92 patients. Aliment Pharmacol Ther 2007;26: Marques P, Maluf-Filho F, Kumar A, et al. Long-term outcomes of acute gastric variceal bleeding in 48 patients following treatment with cyanoacrylate. Dig Dis Sci 2008;53: Brothers MF, Kaufmann JC, Fox AJ, et al. N-butyl 2-cyanoacrylate-- substitute for IBCA in interventional neuroradiology: histopathologic and polymerization time studies. AJNR Am J Neuroradiol 1989;10: Kunstlinger F, Brunelle F, Chaumont P, et al. Vascular occlusive agents. AJR Am J Roentgenol 1981;136: Woodward SC, Herrmann JB, Cameron JL, et al. Histotoxicity of cyanoacrylate tissue adhesive in the rat. Ann Surg 1965;162: Di Stefano DR, de Baere T, Denys A, et al. Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients. Radiology 2005;234: Reprint requests Address requests for reprints to: Bo Jin, MD, PhD, Department of Digestive Diseases, Naval General Hospital, 6 Fucheng Road, Beijing , China. bjbo.jin@gmail.com; fax: (86) ; or Liu-Fang Cheng, MD, Department of Gastroenterology and Hepatology, Chinese People s Liberation Army General Hospital, 28 Fuxing Road, Beijing , China. liufang_cheng@ yahoo.com.cn; fax: (86) Acknowledgments The authors thank Dr James W. Shih from the National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University for his substantial help in the preparation of this paper. Conflicts of interest The authors disclose no conflicts.