Clinical study of endoscopic treatment in patients with gastric varices

2012; 18: 19 25 Clinical study of endoscopic treatment in patients with gastric varices Takayuki Nishi 1, Hiroyasu Makuuchi 1, Soji Ozawa 1, Hideo Shimada 1, Osamu Chino 1, Soichiro Yamamoto 1, Minoru Nakui 1, Akihito Kazuno 1 From 1986 through 2007, endoscopic injection sclerotherapy (EIS) was performed in 67 patients with gastric varices. The total number of treatment sessions was 213: emergency treatment, 16; elective treatment, 125; and prophylactic treatment, 72. Hemostasis was successfully achieved by EIS with Histoacryl blue in all patients who received emergency treatment. Good outcomes were also obtained in patients who underwent elective treatment and prophylactic treatment. The rate of recurrent bleeding was low. Esophageal varices may occur together with gastric varices. These varices serve as a collateral shunt from the portal venous system to the azygos vein and superior vena cava and drain into the left renal vein and inferior vena cava through the adrenal vein. Therefore, gastric varices should be treated at the same time as esophageal varices whenever possible. Sclerotherapy for gastric varices should be performed cautiously, bearing in mind that some varices have a rapid flow rate and large blood volume and that that blood flow cannot be blocked with an endoscopic balloon. EIS with sclerosants and Histoacryl is usually performed for the emergency treatment of actively bleeding gastric varices. EIS is also useful as follow-up treatment to ensure complete eradication of varices. It is important to completely eradicate gastric varices. The goals of treatment for gastric varices are complete eradication and the prevention of recurrence, similar to esophageal varices. KEY WORDS: gastric varices, EIS (endoscopic injection sclerotherapy), cyanoacrylate agents, Histoacryl Nishi T 1, Makuuchi H 1, Ozawa S 1, Shimada H 1, Chino O 1, Yamamoto S 1, Nakui M 1, Kazuno A 1 : Clinical study of endoscopic treatment in patients with gastric varices. JJPH 2012; 18: 19 25 I. INTRODUCTION Esophageal varices are often treated by endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL), and these procedures are now routinely performed by endoscopists. In contrast, the treatment of gastric varices remains challenging. Standard techniques for treatment, including EIS and EVL, have not been established because gastric varices are usually very large and rupture can lead to life-threatening bleeding. Balloon-occluded retrograde transverse obliteration (B-RTO) also has various limitations1). There are some difficult cases that treat with B-RTO because of using massive EOI, having many collateral shunt from the portal venous system. We have long used endoscopic techniques to treat gastric varices2) and have established basic techniques. Good 1 Department of Digestive Surgery, School of Medicine, Tokai University, Boseidai, Isehara-shi, Kanagawa, 259-1193 Japan An abstract of this paper was presented at the 14th General Meeting of the Japan Society of Portal Hypertension in Beppu (2007). Manuscript received March 9, 2009. Manuscript reviced July 7, 2011 outcomes have been obtained. We describe our techniques for the endoscopic treatment of gastric varices and report outcomes in a series of patients. II. SUBJECTS AND METHODS Subjects The study group comprised 67 patients (46 men and 21 women) who underwent EIS for gastric varices at our department from 1986 through 2007. 55 patients had fundal varices, 52 had cardial varices and 15 had both. 22 cases had red spot on varices in 67 cases. Their mean age was 60.0 years (range, 30 to 85). According to the Child-Pugh classification, liver function was Child class A in 40 patients, Child class B in 12, and Child class C in 15. The mean follow-up period was 8.2 months (range, 1 to 90). The mean number of sclerotherapy sessions was 3.2 per patient; the cumulative number of sessions was 213. Ethanol, Aethoxysclerol, ethanolamine oleate, and cyanoacrylate (Histoacryl blue, B/Braun Aesculap, Tuttlingen, Germany) were used for sclerotherapy. 2012; 18: 19 25 19

Sclerotherapy with Histoacryl 1 Preparation (1) An operator and at least two assistants, responsible for treating acute bleeding (2) An endoscope and devices used for sclerotherapy A flexible endoscope with a large aspiration channel that can be used to view the gastric cardia should be selected. Other required materials include a puncture needle (23 gauge), an endoscopic balloon, Histoacryl blue, physiologic saline solution, and thrombin. Massive bleeding can occur during the endoscopic treatment of gastric varices. First, a broad field of vision should be secured to successfully perform sclerotherapy. Recently, devices that allow the delivery of highvolume water jets have become available and are convenient. (3) An electrocardiographic monitor, a blood pressure monitor, a pulse oximeter, emergency medications, and intubation devices are also needed. A Sengstaken-Blakemore tube should also be available in the event of unsuccessful sclerotherapy. In patients with a high risk of bleeding, multiple vessels should be clipped. 2 Technique (1) Patients are placed in the left lateral position to prepare for hematemesis. One ampoule of scopolamine buthylbromide (Buscopan, Japan Boehringer Ingelheim Co., Hyogo, Japan) is given intramuscularly. (2) The throat is anesthetized adequately by applying lidocaine oral solution and spray (Xylocaine Viscous and Xylocaine Spray, AstraZeneca Co., Ltd., Osaka, Japan) several times. The endoscope is inserted slowly to avoid causing the vomiting reflex. (3) The lumen of the esophagus is washed with water and examined, while aspirating excess fluid, and the endoscope is inserted into the stomach after confirming the absence of bleeding from esophageal varices or other sites. The stomach is examined as the endoscope is inserted further. The duodenum is then examined. The scope is returned to the stomach and rotated to closely examine the angle, body, and cardia, and fundus of the stomach. If examination is precluded by blood clots in the gastric fundus, patients should be placed in the right lateral position. Blood clots are thereby moved to the gastric pylorus, facilitating examination of the gastric cardia. (4) Performance of sclerotherapy If gastric variceal bleeding is detected, a puncture needle (23 gauge) is filled with 1 polidocanol (Aethoxysclerol, Sakai Chemical Industry, Osaka, Japan) and is inserted into the variceal wall near the site of bleeding. Puncture sites in patients with variceal bleeding at the cardia along the lesser curvature of the stomach (Lg-c) or at the fundus (Lg-f, Lg-cf) are shown in Fig. 1. After confirming that the needle is properly inserted into the variceal wall, evaluated on the basis of blood reflux, 2 to 3 ml of dehydrated ethanol or 4 to 5 ml of ethanolamine oleate is injected. Then, the inside of the needle is washed with physiological saline solution, and 1 ml of physiological saline solution is aspirated into a 2-ml syringe. While turning the needle upward, 1 ampoule of Histoacryl (0.5 ml) is slowly aspirated and immediately injected. The needle is withdrawn on completion of the injection. (5) If it is unclear whether the intravenous injection was Bleeding site Bleeding site A: The injection site in patients with cardiac variceal bleeding located in the lesser curvature of the stomach (Lg-c) B: The injection site in patients with fundal variceal bleeding (Lg-f, Lg-cf). Injection site of first choice, Second choice when the initial injection is inadequate Fig. 1 Sclerotherapy with Histoacryl for gastric variceal bleeding (Makuuchi H: Sclerotherapy for gastric varices. Illustrated guide to sclerotherapy for esophageal varices. Igakushoin, Tokyo, 1988, 104 105; Makuuchi H, Machimura T, Shimada H, et al: Special edition: esophagogastric varices 3. Treatment of gastric varices (2) emergency hemostasis. Clin Gastroenterol 1995; 10: 647 654) 20 2012; 18: 19 25

properly performed, Histoacryl is injected after injecting 2 to 3 ml of 1 Aethoxysklerol. (6) Air and blood are aspirated from the stomach as extensively as possible, and the endoscope is removed. (7) Aluminum hydroxide plus magnesium hydroxide suspension (Maalox, Astellas Pharmaceutical Co., Ltd., Tokyo Japan), sodium alginate (Alloid G, Kaigen Co., Ltd., Osaka, Japan), and a proton-pump inhibitor are administered. (8) Additional sclerotherapy for gastric varices Intravariceal injection is repeated after 1 week. If blood reflux is evident, treatment is repeated as described above. After 2 weeks, 2 to 3 ml of 1 Aethoxysklerol is injected around the gastric cardia (Fig. 2). 3 Follow-up at outpatient clinic after sclerotherapy (1) Unlike the esophagus, aggressive factors such as hydrochloric acid and pepsin are present in the stomach. Therefore, antacids, mucosal protective agents, and proton-pump inhibitors are given continuously. (2) Endoscopy is performed at 6-month intervals to confirm the presence or absence of the recurrence of varices. If varices recur, additional sclerotherapy is performed immediately. (3) It is essential that liver function is maintained. Liver function is tested regularly, and liver-protective agents and amino-acid preparations are given. Patients should be instructed to intake a well-balanced diet, abstain from drinking alcohol, avoid overwork, and maintain a regular lifestyle. (4) Alpha-fetoprotein levels are measured and abdominal ultrasonography is performed at regular intervals to screen for liver cancer. III. RESULTS EIS was performed in 67 patients with gastric varices at our department. The number of initial treatment session was 67: emergency treatment, 10; elective treatment, 37, and prophylactic treatment, 20. The cumulative number of treatment sessions was 213: emergency treatment, 16; elective treatment, 125, and prophylactic treatment, 72. In all patients who received emergency treatment, hemostasis was successfully achieved by EIS with Histoacryl. However, 1 patient had recurrent bleeding after 2 days, and hemostasis was achieved by repeated sclerotherapy; however, the patient died of hepatic failure after 2 weeks. Among patients receiving elective treatment, 3 (2.4 ) had varices bleeding, and hemostasis was achieved by sclerotherapy. No patient died of bleeding. However, 1 patient with pancreatic cancer died after 9 months, and 1 patient with liver cancer died after 2 years. Among patients receiving prophylactic treatment, 2 (2.8 ) had recurrent bleeding at the second session of sclerotherapy, but hemostasis was achieved by sclerotherapy. No patient died of bleeding. However, 1 patient with liver cancer died after 1 year, and 1 patient with liver failure died after 2 years. Th First session: The thickest vein in punctured, and sclerotherapy is pe injection is further performed at 2 First session: The thickest vein in the gastric cardia is punctured, and sclerotherapy is performed. Intravariceal injection is further performed at 2 to 3 sites. Second session: Intravariceal inject Second session: Intravariceal injection is performed Third session: Aliquots of 3 ml of 1 Aethoxysklerol are injected at sites of folds. The site of puncture Fig. 2 Additional sclerotherapy for gastric variceal bleeding (Makuuchi H: Sclerotherapy for gastric varices. Illustrated guide to sclerotherapy for esophageal varices. Igakushoin, Tokyo, 1988, 104 105; Makuuchi H, Machimura T, Shimada H, et al: Special edition: esophagogastric varices 3. Treatment of gastric varices (2) emergency hemostasis. Clin Gastroenterol 1995; 10: 647 654) 2012; 18: 19 25 21

Many recurrent bleeding cases had intra mucosal venous dilatation (IMVD). We performed follow-up upper gastrointestinal endoscopy twice a year such cases and did additional EIS as soon as possible. IV. CASE PATIENT The patient was a 58-year-old man who was receiving treatment for type C hepatitis and liver cirrhosis. Followup upper gastrointestinal endoscopy revealed linear, small (F 1 ) varices with red-color signs at the right-side wall of the lower esophagus. When the scope was rotated in the stomach, nodular or tumorous (F 3 ) varices were seen in the gastric cardia (Fig. 3). Sclerotherapy with Histoacryl was performed to treat the gastric as well as esophageal varices (Fig. 4). Endoscopy performed after 2 weeks showed that the esophagogastric varices had become fibrous scar tissue, with no bleeding (Fig. 5). V. DISCUSSION EIS and EVL, now widely used to treat esophageal varices, have improved outcomes. Treatment strategies for esophageal varices have generally been established. However, gastric varices have a high risk of massive bleeding, which may be life threatening. Apart from EIS and EVL, B-RTO has been reported to be useful for the treatment of gastric varices. Sclerotherapy for gastric varices was first performed by Makuuchi. We perform EIS with Histoacryl, a cyanoacrylate agent, at our department. Obara et al. proposed that the ideal treatment for gastric varices should be safe, minimally invasive, very effective, and able to be completed within a short time, with no risk of recurrence. They reported that endoscopic treatment with cyanoacrylate agents meets these conditions 3) (Fig. 6). In 1987, Soehendra et al. first used Histoacryl to treat 4 patients with gastric varices and achieved stable hemostasis 4). In Japan, Suzuki et al. used Histoacryl in 2 patients with gastric variceal bleeding; hemostasis was achieved in both A B C D Fig. 3 Esophagogastric varices. A, B: Linear, small (F 1 ) varices of the esophagus, C, D: Cardiac varices (Lg-c) that are nodular or tumorous (F 3 ). 22 2012; 18: 19 25

A B C D Fig. 4 Sclerotherapy with Histoacryl for gastric varices. A B: Sclerotherapy with Histoacryl for cardiac varices (Lg-c). patients 5). Histoacryl requires 200 seconds to polymerize after contact with water, but polymerizes immediately after contact with blood. In contrast, Aron Alfa A (ToaGosei Co., Ltd., Tokyo, Japan), a cyanoacrylate agent, requires 5 to 20 seconds to polymerize after contact with water and 10 to 40 seconds to polymerize after contact with blood. Histoacryl is considered the most suitable agent for gastric varices with a large, rapid blood flow because it polymerizes instantly on contact with blood. Yamamoto et al. used this property of Histoacryl to develop the sandwich method, in which gastric varices are filled with physiological saline solution before and after the injection of Histoacryl 6). In patients that require emergency therapy for acute gastric variceal bleeding, Histoacryl can be 7, 8). used as first-line treatment Because esophageal and gastric varices serve as a collateral shunt from the portal venous system to the azygos vein and superior vena cava, these varices are likely to occur together. Makuuchi et al. reported that 202 (48.4 ) of 431 patients with esophageal varices (excluding 14 patients who were lost to follow-up) also had gastric varices. Moreover, 42 (34.7 ) of 138 patients who had esophageal varices with a history of bleeding (excluding 17 patients who were lost to follow-up) had gastric variceal bleeding 9). These findings show that esophageal varices are closely related to gastric varices and that the risk of complications such as bleeding is increased in patients with both types of varices. In patients with gastric varices complicated by esophageal varices, it is essential that the esophageal varices are also treated. Basically, treatment for gastric varices involves intravariceal injection to eradicate the varices and submucosal injection to 2012; 18: 19 25 23

A B C D Fig. 5 Esophagogastric varices after sclerotherapy. A, B: Esophageal varices after sclerotherapy, C, D: Cardiac varices (Lg-c) after sclerotherapy. prevent recurrence, similar to esophageal varices. However, the following differences from esophageal varices should be borne in mind when sclerotherapy is performed for gastric varices: (1) gastric varices usually have a large, rapid blood flow, and (2) blood flow cannot be blocked in gastric varices. Treatment techniques for gastric varices include (1) the reflux method, in which the esophageal varix is punctured, and the sclerosant is allowed to reflux into the gastric varix, with the help of an endoscopic balloon; and the direct puncture method, in which the endoscope is rotated, the needle is inserted directly into the gastric varix, and the sclerosant is injected. The following precautions should be taken when performing sclerotherapy for gastric varices: (1) Esophageal varices should be treated at the same time as gastric varices. (2) Cardiac varices (Lg-c) located inferior to the esophagogastric junction can be treated by the regurgitation method after esophageal varices are punctured. (3) Varices located far from the esophagogastric junction (Lg-cf) and fundal varices (Lg-f) should be treated by the direct puncture method (Fig. 2). (4) Varices with slow blood flow can be treated by sclerotherapy with 5 ethanolamine oleate or dehydrated ethanol. (5) Sclerotherapy with Histoacryl should be used to treat varices with rapid blood flow. (6) Similar to esophageal varices, the goals of treatment for gastric varices are complete eradication of the varices and the promotion of fibrosis from the gastric cardia to the fundus (Fig. 3). VI. CONCLUSIONS 1. Various treatments can be used to manage gastric varices. EIS with Histoacryl is the treatment of first choice for acute bleeding from gastric varices. 2. B-RTO or EIS is usually performed as additional treatment. We recommend EIS. 3. The ultimate goals of treatment for gastric varices are complete eradication and the prevention of recurrence, similar to esophageal varices. 24 2012; 18: 19 25

Patients with variceal bleeding Patients receiving elective andprophylactic treatment Renal-vein shunt (-) or (+) Shunt-induced encephalopathy (-) Renal-vein shunt (+) Shunt-induced encephalopathy (+) Good liver function Splenectomy required Varices 12 mm or more in diameter BRTO (+splenic arterialembolization) Endoscopic treatment Combination of CA and EO EVL + EIS Sclerotherapy with CA during occlusion of the gastro-renal shunt (SO-EIS) Hassab's operation Severe liver dysfunction CA, EVLs *CA: cyanoacrylate, EO: ethanolamine oleate, EVL: endoscopic variceal ligation, EIS: endoscopic injection sclerotherapy, SO-EIS: shunt-occluded endoscopic injection sclerotherapy, B-RTO: balloon-occluded retrograde transvenous obliteration. Fig. 6 Treatment Strategies for Gastric Varices*. This figure was presented at the symposium Treatment Strategies for Gastric Varices, which was chaired by Katsutoshi Obara and Nobuo Murata, at the Japan Digestive Disease Week held in 2004 (Fukuoka). REFERENCES 1 Obara K: Gastric varices: EIS vs. B-RTO. Jpn J Portal Hypertens 2006; 12: 281 284 2 Mitomi T, Tanaka Y, Makuuchi H: Treatment of esophagogastric variceal bleeding. Surg Diagn & Treat 1983; 25: 1479 1484 3 Obara K: The best treatment for gastric varices. Jpn J Portal Hypertens 1999; 5: 3 5 4 Soehendra, N, Grimm H, Nam VC, et al: N-butyl-2- cyanoacrylate: a supplement to endoscopic sclerotherapy. Endoscopy 1987; 19: 221 224 5 Suzuki H, Yamamoto M, Chibai M, et al: Sclerotherapy with Histoacryl for gastric varices: progress in gastrointestinal endoscopy 1988; 33: 83 86 6 Yamamoto M, Suzuki H, Chibai M, et al: Endoscopic sclerotherapy with Histoacryl. Gastrointest Endosc 1989; 1: 851 857 7 Obara K: Current status of treatment for gastric varices: treatment of gastric varices. Gastroenterol Endosc 2005; 47: 356 365 8 Obara K, Sakamoto H, Takiguchi F, et al: Emergency and elective sclerotherapy for cardiac variceal (Lg-c, Lg-cf) bleeding. Gastrointest Endosc 1991; 3: 1435 1443 9 Makuuchi H, Machimura T, Mizutani G, et al: Clinical significance of sclerotherapy for gastric varices. Gastrointest Endosc 1991; 3: 1417 1425 10 Makuuchi H: Sclerotherapy for gastric varices. Illustrated guide to sclerotherapy for esophageal varices. Igakushoin, Tokyo, 1988, 104 105 11 Makuuchi H, Machimura T, Shimada H, et al: Special edition: esophagogastric varices 3. Treatment of gastric varices (2) emergency hemostasis. Clin Gastroenterol 1995; 10: 647 654 2012; 18: 19 25 25