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Retrograde Transvenous Obliteration of Gastric Varices Associated with Large Collateral Veins or a Large Gastrorenal Shunt
Retrograde Transvenous Obliteration of Gastric Varices Associated with Large Collateral Veins or a Large Gastrorenal Shunt Kazuya Sugimori, MD, Manabu Morimoto, MD, Kazuhito Shirato, MD, Atsushi Kokawa, MD, Naohiko Tomita, MD, Kazushi Numata, MD, Toshifumi Saito, MD, and Katsuaki Tanaka, MD Balloon-occluded retrograde transvenous obliteration of gastric varices by a microcatheter insertion method was performed in eight patients with large collateral veins or a large gastrorenal shunt. A 3-F microcatheter was selectively inserted into the gastric varices through a 6-F balloon catheter wedged in the left adrenal vein. Selective venography of the gastric varices and injection of the sclerosing agent, a mixture of 10% ethanolamine oleate and iopamidol, through the microcatheter system without occluding the collateral veins was accomplished in one treatment session in all patients. There have been no complications or recurrences of gastric varices in any of the patients during the follow-up period. J Vasc Interv Radiol 2005; 16:113–118
ENDOSCOPIC injection sclerotherapy is currently the mainstay of treatment in the management of esophageal varices (1). However, gastric fundal varices located in the fornix cannot be effectively treated by endoscopic injection sclerotherapy (2–5) because of the rapid loss of sclerosing agent as a result of the rapid blood flow in such varices, and they are associated with mortality rates as high as 45% (3) when they rupture. A transjugular intrahepatic portosystemic shunt procedure has been widely used for gastric fundal varices (6), but it does not always result in regression of the varices (7), and a transjugular intrahepatic portosystemic shunt procedure cannot always be recommended for patients with severe hepatic encephalopathy
From the Gastroenterological Center, Yokohama City University Medical Center, 4 –57 Urafune-cho, Minami-ku, Yokohama 232– 0024, Japan. Received May 13, 2004; revision requested June 24; revision received August 10; accepted August 11. Address correspondence to K.T.; E-mail: k_tanaka@ urahp.yokohama-cu.ac.jp None of the authors have identified a conflict of interest. © SIR, 2005 DOI: 10.1097/01.RVI.0000143765.38128.23
because of possible aggravation of the encephalopathy (8 –10). In 1996, balloon-occluded retrograde transvenous obliteration was described by Kanagawa et al (11) as a minimally invasive interventional radiologic procedure for occlusion of gastric varices through a gastrorenal shunt, and satisfactory results have been reported in patients with gastric varices (12–15) and hepatic encephalopathy (16,17). However, the technical success rates of the initial procedure were unsatisfactory, with rates of only 57% reported by Sonomura et al (18) and 56% by Fukuda et al (19), and two or more treatment sessions were often required to complete treatment, resulting in longer hospitalization. According to the results of adrenal venography during balloon occlusion, the gastric varices were often not opacified in patients who had many large collateral veins or a large gastrorenal shunt. Occlusion of the collateral veins is essential for successful obliteration of the gastric varices in such patients, and they were treated by injection of a sclerosing agent or by insertion of spring coils through a microcatheter during selective catheterization. These procedures were often repeated one or more times before the gastric varices were occluded. Hirota
et al (14) found that the number of sessions required to obliterate varices was directly proportional to the grade of collateral development. In the present study, we developed a method in which a microcatheter is selectively inserted into gastric varices through a 6-F balloon catheter wedged in the left adrenal vein and found that it could be used to successfully treat gastric varices associated with many large collateral veins and/or a large gastrorenal shunt in one treatment session without occlusion of the collateral veins. The purpose of this study was to evaluate the clinical efficacy and complications associated with balloonoccluded retrograde transvenous obliteration of gastric varices by the microcatheter insertion method.
MATERIALS AND METHODS Patients Between March 2001 and December 2003, 15 patients with cirrhosis and gastric varices were admitted to our institution. The criteria for entry into this study were (i) the presence of bleeding fundic gastric varices or risk of rupture of gastric varices with a red color sign observed endoscopically, (ii) demonstration of a gastrorenal
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shunt by contrast material– enhanced computed tomography (CT), and (iii) incomplete opacification of the gastric varices on left adrenal venography. Seven patients were excluded from the study and eight patients (six men and two women; age range, 48 –74 years) were enrolled. Six patients had bleeding gastric varices 3–27 days before the procedure, and the remaining two patients had a risk of rupture of their gastric varices. The gastric varices were classified based on gastroendoscopic criteria according to the system adopted in Japan (20,21): Lg-c, adjacent to the cardiac ring; Lg-f, separated from the cardiac ring; and Lg-cf, extending from the cardiac ring to the gastric fundus. Four patients’ varices were classified as Lg-f (Figure, part a), and the varices of the other four patients were classified as Lg-cf. Two patients had been treated for esophageal varices by endoscopic injection sclerotherapy or endoscopic variceal ligation. Six patients had hepatitis C viral infection and two patients had non-B, non-C viral infection. Hepatic function was classified as class A by the ChildPugh system in three patients and as class B in the other five patients. Two patients had hepatocellular carcinoma as a complication. Because no institutional review board existed at our institution at the time the study was initiated, the study was performed according to the guidelines of the Helsinki Declaration. Written informed consent was obtained from all patients and from relatives. Procedure The connection of the gastric varices to the left adrenal vein through a gastrorenal shunt and the diameter of the shunt were selected before the procedure based on the contrast material– enhanced CT findings (High-Speed Advantage RP; GE Yokogawa Medical Systems, Tokyo, Japan). The nonionic contrast material iopamidol (100 –150 mL Iopamiron; Nippon Schering, Osaka, Japan) was administered at a rate of 3 mL/sec, and dual-phase CT images were obtained. The contrast material– enhanced CT scan revealed that one of the varicose veins around the gastric fornix coursed posteriorly and caudally to empty into the inferior phrenic vein, which in turn connected to the left adrenal vein (Figure, part b).
Before performing balloon-occluded retrograde transvenous obliteration, we obtained celiac and superior mesenteric angiograms to confirm the anatomy of the gastric varices (Figure, part c). Next, a 6-F balloon catheter with a balloon diameter of 20 mm (Selecon balloon catheter; Clinical Supply, Gifu, Japan) was inserted through the right femoral vein or right internal jugular vein into the left adrenal vein and wedged in it. Left adrenal venography with 20 mL of iopamidol was performed with the balloon inflated, but the gastric varices were not completely opacified in any of the patients because of blood flow from the gastric varices into the dilated collateral veins, such as the inferior phrenic vein or pericardiacophrenic vein. We then inserted a 3-F microcatheter and performed selective catheterization of the gastric varices through a 6-F balloon catheter during balloon occlusion of the left adrenal vein. After insertion of the microcatheter into the gastric varices, it was flushed with contrast medium (iopamidol) to confirm that it filled the gastric varices and to measure the volume injected. The sclerosing agent, a mixture of 10% ethanolamine oleate (Odamin; Mochida Pharmaceutical, Tokyo, Japan) and the same dose of iopamidol, was injected slowly under fluoroscopic monitoring until the gastric fundal varices had been completely filled. A 20-mL volume of 50% glucose was injected through the microcatheter before injection of the sclerosing agent as a means of washing out any blood cells in the gastric varices (13). The maximum dose of the ethanolamine oleate/iopamidol mixture used at one time depended on the volume of gastric varices; however, in most patients, it was less than 20 mL. The ethanolamine oleate/iopamidol mixture remained in the varices for 15–17 hours (overnight) after injection with the occlusion balloon inflated. As much of the ethanolamine oleate/iopamidol mixture as possible was then withdrawn under fluoroscopic observation, and the procedure was terminated when a test injection of contrast medium (iopamidol) demonstrated that clots had formed in the varices. Blood pressure, pulse rate, electrocardiogram, arterial oxygen saturation (pulse oximeter), and urine volume were monitored throughout the proce-
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dure. Intravenous administration of 4,000 U of human haptoglobin (Green Cross, Osaka, Japan) during the procedure was used to prevent hemolysis and subsequent renal failure that may be induced by ethanolamine oleate (22). Follow-up Follow-up endoscopy and CT were performed at 1 week and 3 months after the balloon-occluded retrograde transvenous obliteration procedure and every 3 or 6 months thereafter, and hepatic function and blood cell counts were monitored monthly throughout the follow-up period. Technical success was defined by (i) complete clotting of the gastric varices as demonstrated by CT and (ii) disappearance of the gastric varices or reduced variceal size endoscopically.
RESULTS The Table summarizes the results of the balloon-occluded retrograde transvenous obliteration of gastric varices by the microcatheter insertion method. Left adrenal venography with 20 mL of iopamidol was performed with the balloon inflated, but the gastric varices were not opacified in any of the patients (Figure, part d). There were many large collateral veins, the inferior phrenic veins were observed in all patients, and the hemiazygos vein and/or pericardiacophrenic vein was observed in four patients. Selective catheterization of the gastric varices and subsequent venography were performed in all patients with the microcatheter without occlusion of the collateral veins (Figure, part e), and the gastric varices were filled with 8.5–28 mL of the ethanolamine oleate/ iopamidol mixture (Figure, part f). Technical success was achieved in one treatment session in all patients, and no major side effects were observed. All patients reported fever, and transient hemoglobinuria was observed during the procedure, but these symptoms had almost disappeared by the end of treatment. Hepatic function parameters did not change during or after the procedure. The serum amylase level of one patient was increased 1 week after the procedure, but it returned to within the normal range within 4 days after therapy. The length
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Figure. Gastric varices with collateral veins and a large gastrorenal shunt in a 71-year-old woman with bleeding gastric varices. (a) Endoscopic examination revealed huge gastric fundal varices with a red spot on the varices. (b) Contrast material– enhanced CT shows marked dilation of the gastric varices (arrows). (c) Celiac angiogram reveals marked dilation of the gastric varices (arrowheads), followed by a gastrorenal shunt (arrows), the left renal vein (LRV), splenic vein (SV), portal vein (PV), and inferior vena cava (IVC). (d) Left adrenal venography performed during 6-F balloon catheter occlusion (20 mm in diameter) shows the markedly dilated gastrorenal shunt (white arrowheads) and the inferior phrenic vein (arrow) and pericardiacophrenic veins (arrowhead), but no gastric varices are visible. (e) A 3-F microcatheter was inserted into the gastric varices through a 6-F balloon catheter wedged in the left adrenal vein. The arrow shows the tip of the microcatheter inserted into the gastric varices. Gastric variceal venography shows that the gastric varices are filled with contrast medium, but no collateral veins are seen. (f) Gastric varices are filled with the ethanolamine oleate/iopamidol mixture. (continues)
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ance of the varices 1 week after the procedure, but follow-up endoscopy 3 months after the procedure revealed disappearance of the gastric varices in seven of the patients and reduced variceal size in the other patient (Figure, part h). No recurrence or bleeding of gastric varices developed in any of the patients during the 3–36month follow-up period (mean, 13 months). Esophageal varices developed in four patients, and endoscopic variceal ligation was successful. One patient was found to have a hepatocellular carcinoma lesion 10 months after the procedure and was successfully treated with radiofrequency ablation therapy.
DISCUSSION
Figure. (continued) (g) One week after the procedure, contrast-enhanced CT shows that the gastric varices have been completely obliterated (arrows). (h) Follow-up endoscopy 3 months after the procedure reveals disappearance of the gastric varices.
of hospital stay ranged from 9 days to 20 days (mean, 14 days). The two patients who underwent the procedure for prevention had a shorter hospital stay (9 days each) than those with bleeding varices. One week after the procedure, contrast-enhanced CT showed gastric varices as areas of nonenhancement in all cases, meaning that clot formation had occurred (Figure, part g). There were no changes in the endoscopic appear-
Balloon-occluded retrograde transvenous obliteration has been used as a new radiologic modality for the treatment of gastric varices (1), and a very high initial success rate of obliteration of gastric varices has been reported (11–15). However, the technical success rate of the initial procedure was unsatisfactory, and two or more treatment sessions were often required to complete treatment (18,19), resulting in longer hospitalization. In the present study, we used a microcatheter insertion method in the procedure for balloon-occluded retrograde transvenous obliteration of gastric varices, and the results showed a very high initial success rate (100%) for obliteration of gastric varices in a single treatment session. As gastric varices progress, a gastrorenal shunt and/or collateral veins such as the inferior phrenic, hemiazygos, or pericardiacophrenic veins develop according to the degree of blood flow from the gastric varices, and occlusion of these collateral veins is essential to obliterate the gastric varices (14,18). Hirota et al (14) classified the degree of progression of gastric varices and collateral veins into five grades based on the adrenal venography findings during balloon occlusion: grade 1, no collateral veins; grade 2, small collateral veins; grade 3, a few collateral veins of medium to large size; grade 4, many large collateral veins; and grade 5, no occlusion of the left adrenal vein as a result of a very large gastrorenal shunt with rapid blood flow. Occlusion of the collateral
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veins is the essential first step in the treatment of patients with gastric varices of grade 3 or worse, and the investigators occluded these collateral veins with an injection of sclerosing agent or spring coils inserted through a microcatheter and selective catheterization (14). However, even when the collateral veins were occluded, the very large gastric varices could not be obliterated in a single treatment session through the occlusion balloon inflated in the adrenal vein, and second and third balloon-occluded retrograde transvenous obliteration procedures were often needed. In this study, we used a method of microcatheter insertion into gastric varices and found that the procedure was superior to the conventional approach. A balloon catheter was wedged in the adrenal vein, and the sclerosing agent was injected through the inflated balloon occlusion catheter. Advantages of our methods include (i) the fact that occlusion of collateral veins is not required to complete treatment and (ii) the use of a low dose of sclerosing agent. The first advantage is based on the fact that, despite the majority of our patients having Hirota (14) grade 4 gastric varices with many large collateral veins, it was easy to occlude the varices in one treatment session by the microcatheter insertion method without occluding the collateral veins. The technical success of the initial procedure by the microcatheter insertion method resulted in clearly shorter hospital stays (mean, 14 days) compared with the mean length of stay for conventional balloon-occluded retrograde transvenous obliteration of gastric varices (27 days) (15). The second advantage arises from the fact that the dose used for our selective obliteration of gastric varices (8.5–28 mL) was much lower than the 30 mL maximum dose of ethanolamine oleate/iopamidol mixture reported by Hirota et al (14), the 60 mL reported by Koito et al (12) and Sonomura et al (18), and the 62 mL reported by Akahane et al (13) for each session of conventional balloon-occluded retrograde transvenous obliteration of gastric varices. The lower dose may have reduced the complications associated with the procedure of balloon-occluded retrograde transvenous obliteration of gastric varices.
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Results of Balloon-occluded Retrograde Transvenous Obliteration of Gastric Varices by the Microcatheter Insertion Method Left Adrenal Venography Pt. No.
Endoscopic Classification*
Diameter of Gastrorenal Shunt (mm)
1† 2‡ 3‡ 4 5‡ 6 7‡ 8
Lg-cf Lg-f Lg-f Lg-cf Lg-f Lg-cf Lg-f Lg-cf
28 32 22 19 22 15 13 16
Collateral Veins IPV, IPV, IPV, IPV, IPV, IPV, IPV, IPV,
HAV PCV PCV HAV PCV, HAV HAV HAV HAV
Gastric Varices after Treatment
Dose of Ethanolamine Oleate (mL)
Endoscopy
CT
Follow-up (mo)
8.5 15 20 19 28 20 17.5 20
Reduced Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared
Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared
36 18 26 5 7 4 3 3
Note.—HAV ⫽ hemiazygos vein; IPV ⫽ inferior phrenic vein; PCV ⫽ pericardiacophrenic vein. * See text for explanation (20, 21). † A hepatocellular carcinoma lesion was detected 10 months after the procedure and was successfully treated by radiofrequency ablation therapy. ‡ Esophageal varices were aggravated during the follow-up period, and successful endoscopic variceal ligation was performed.
Transjugular intrahepatic portosystemic shunts are commonly used to treat gastric varices, but 50% of fundic gastric varices fail to resolve after the procedure (7), and they may induce or aggravate hepatic encephalopathy (8 – 10). The balloon-occluded retrograde transvenous obliteration procedure, conversely, blocks gastric variceal blood flow with a very high success rate. Because gastrorenal shunts decrease portal venous pressure, their obliteration may cause portal venous pressure to increase and new collateral veins to the esophageal varices to develop, and four of our patients did in fact experience exacerbation of esophageal varices after balloon-occluded retrograde transvenous selective obliteration. Therefore, our procedure is likely to be a temporizing procedure for patients who are not candidates for a transjugular intrahepatic portosystemic shunt. We recommend it for patients who have progressive fundic gastric varices at risk of rupture and associated with a gastrorenal shunt or hepatic encephalopathy. In conclusion, balloon-occluded retrograde transvenous selective obliteration by the microcatheter insertion method is an effective treatment for progressive gastric varices with large collateral veins or a large gastrorenal shunt.
References 1. Binmoeller KF, Borsatto R. Variceal bleeding and portal hypertension. Endoscopy 2000; 32:189 –199. 2. Idezuki Y. Present status of sclerotherapy and surgical treatment for esophageal varices in Japan. Japanese Research Society for Portal Hypertension and Japanese Research Society for Sclerotherepy of Esophageal Varices. World J Surg 1992; 16:1193–1201. 3. Sarin SK, Sachdev G, Nanda R, Misra SP, Broor SL. Endoscopic sclerotherapy in the treatment of gastric varices. Br J Surg 1988; 75:747–750. 4. Sandy H. The role of sclerotherapy in the treatment of esophageal varices: personal experience and a review of randomized trials. Am J Gastroenterol 1987; 82:813– 822. 5. Korula L, Chin K, Ko Y, Yamada S. Demonstration of two distinct subsets of gastric varices: observations during a seven-year study of endoscopic sclerotherapy. Dig Dis Sci 1991; 36:303– 309. 6. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval shunt: an experimental study. Radiology 1969; 92:1112– 1114. 7. Sanyal AJ, Freedman AM, Luketic VA, et al. The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts. Gastroenterology 1997; 112:889 – 898. 8. Kerlan RK Jr, LaBerge JM, Baker EL, et al. Successful reversal of hepatic encephalopathy with intentional occlusion of transjugular intrahepatic porto-
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systemic shunts. J Vasc Interv Radiol 1995; 6:917–921. Brown RS Jr., Lake JR. Transjugular intrahepatic portosystemic shunt as a form of treatment for portal hypertension: indication and contraindications. Adv Intern Med 1997; 42:485–504. Somberg KA. TIPS: safe, effective, better? [editorial]. Am J Gastroenterol 1997; 92:1412–1416. Kanagawa H, Mima S, Kouyama H, Gotoh K, Uchida T, Okuda K. Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol 1996; 11:51–58. Koito K, Namieno T, Nagakawa T, Morita K. Balloon-occluded retrograde transvenous obliteration for gastric varices with gastrorenal or gastrocaval collaterals. AJR Am J Roentgenol 1996; 167:1317–1320. Akahane T, Iwasaki T, Kobayashi N, et al. Changes in liver function parameters after occlusion of gastrorenal shunts with balloon-occluded retrograde transvenous obliteration. Am J Gastroenterol 1997; 92:1026 –1030. Hirota S, Matsumoto S, Tomita M, Sako M, Kono M. Retrograde transvenous obliteration of gastric varices. Radiology 1999; 211:349 –356. Matsumoto A, Hamamoto N, Nomura T, et al. Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices. Am J Gastroenterol 1999; 94:643– 649. Kawanaka H, Ohta M, Hashizume M, et al. Portosystemic encephalopathy treated with balloon-occluded retro-
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grade transvenous obliteration. Am J Gastroenterol 1995; 90:508 –510. 17. Numata K, Tanaka K, Kiba T, et al. Use of balloon-occluded retrograde transvenous obliteration with ethanolamine oleate for the treatment of hepatic encephalopathy in a cirrhotic patient with a large spontaneous splenorenal shunt. J Gastroenterol 1998; 33:424 – 427. 18. Sonomura T, Sato M, Kishi K, et al. Balloon-occluded retrograde trans-
venous obliteration for gastric varices: a feasibility study. Cardiovasc Intervent Radiol 1998; 21:27–30. 19. Fukuda T, Hirota S, Sugimura K. Long-term results of balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy. J Vasc Interv Radiol 2001; 12:327–336. 20. Idezuki Y. General rules for recording endoscopic findings of esophagogastric varices (1991). Japanese Society
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for Portal Hypertension. World J Surg 1995; 19:420 – 422. 21. Hashizume M, Kitano S, Yamaga H, Koyanagi N, Sugimachi K. Endoscopic classification of gastric varices. Gastrointest Endosc 1990; 36:276 –280. 22. Miyoshi H, Oshiba S, Matsumoto A, Takada K, Umegaki E, Hirata I. Haptoglobin prevents renal dysfunction associated with intravariceal infusion of ethanolamine oleate. Am J Gastroenterol 1991; 86:1638 –1641.
ENDOSCOPIC injection sclerotherapy is currently the mainstay of treatment in the management of esophageal varices (1). However, gastric fundal varices located in the fornix cannot be effectively treated by endoscopic injection sclerotherapy (2–5) because of the rapid loss of sclerosing agent as a result of the rapid blood flow in such varices, and they are associated with mortality rates as high as 45% (3) when they rupture. A transjugular intrahepatic portosystemic shunt procedure has been widely used for gastric fundal varices (6), but it does not always result in regression of the varices (7), and a transjugular intrahepatic portosystemic shunt procedure cannot always be recommended for patients with severe hepatic encephalopathy
From the Gastroenterological Center, Yokohama City University Medical Center, 4 –57 Urafune-cho, Minami-ku, Yokohama 232– 0024, Japan. Received May 13, 2004; revision requested June 24; revision received August 10; accepted August 11. Address correspondence to K.T.; E-mail: k_tanaka@ urahp.yokohama-cu.ac.jp None of the authors have identified a conflict of interest. © SIR, 2005 DOI: 10.1097/01.RVI.0000143765.38128.23
because of possible aggravation of the encephalopathy (8 –10). In 1996, balloon-occluded retrograde transvenous obliteration was described by Kanagawa et al (11) as a minimally invasive interventional radiologic procedure for occlusion of gastric varices through a gastrorenal shunt, and satisfactory results have been reported in patients with gastric varices (12–15) and hepatic encephalopathy (16,17). However, the technical success rates of the initial procedure were unsatisfactory, with rates of only 57% reported by Sonomura et al (18) and 56% by Fukuda et al (19), and two or more treatment sessions were often required to complete treatment, resulting in longer hospitalization. According to the results of adrenal venography during balloon occlusion, the gastric varices were often not opacified in patients who had many large collateral veins or a large gastrorenal shunt. Occlusion of the collateral veins is essential for successful obliteration of the gastric varices in such patients, and they were treated by injection of a sclerosing agent or by insertion of spring coils through a microcatheter during selective catheterization. These procedures were often repeated one or more times before the gastric varices were occluded. Hirota
et al (14) found that the number of sessions required to obliterate varices was directly proportional to the grade of collateral development. In the present study, we developed a method in which a microcatheter is selectively inserted into gastric varices through a 6-F balloon catheter wedged in the left adrenal vein and found that it could be used to successfully treat gastric varices associated with many large collateral veins and/or a large gastrorenal shunt in one treatment session without occlusion of the collateral veins. The purpose of this study was to evaluate the clinical efficacy and complications associated with balloonoccluded retrograde transvenous obliteration of gastric varices by the microcatheter insertion method.
MATERIALS AND METHODS Patients Between March 2001 and December 2003, 15 patients with cirrhosis and gastric varices were admitted to our institution. The criteria for entry into this study were (i) the presence of bleeding fundic gastric varices or risk of rupture of gastric varices with a red color sign observed endoscopically, (ii) demonstration of a gastrorenal
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shunt by contrast material– enhanced computed tomography (CT), and (iii) incomplete opacification of the gastric varices on left adrenal venography. Seven patients were excluded from the study and eight patients (six men and two women; age range, 48 –74 years) were enrolled. Six patients had bleeding gastric varices 3–27 days before the procedure, and the remaining two patients had a risk of rupture of their gastric varices. The gastric varices were classified based on gastroendoscopic criteria according to the system adopted in Japan (20,21): Lg-c, adjacent to the cardiac ring; Lg-f, separated from the cardiac ring; and Lg-cf, extending from the cardiac ring to the gastric fundus. Four patients’ varices were classified as Lg-f (Figure, part a), and the varices of the other four patients were classified as Lg-cf. Two patients had been treated for esophageal varices by endoscopic injection sclerotherapy or endoscopic variceal ligation. Six patients had hepatitis C viral infection and two patients had non-B, non-C viral infection. Hepatic function was classified as class A by the ChildPugh system in three patients and as class B in the other five patients. Two patients had hepatocellular carcinoma as a complication. Because no institutional review board existed at our institution at the time the study was initiated, the study was performed according to the guidelines of the Helsinki Declaration. Written informed consent was obtained from all patients and from relatives. Procedure The connection of the gastric varices to the left adrenal vein through a gastrorenal shunt and the diameter of the shunt were selected before the procedure based on the contrast material– enhanced CT findings (High-Speed Advantage RP; GE Yokogawa Medical Systems, Tokyo, Japan). The nonionic contrast material iopamidol (100 –150 mL Iopamiron; Nippon Schering, Osaka, Japan) was administered at a rate of 3 mL/sec, and dual-phase CT images were obtained. The contrast material– enhanced CT scan revealed that one of the varicose veins around the gastric fornix coursed posteriorly and caudally to empty into the inferior phrenic vein, which in turn connected to the left adrenal vein (Figure, part b).
Before performing balloon-occluded retrograde transvenous obliteration, we obtained celiac and superior mesenteric angiograms to confirm the anatomy of the gastric varices (Figure, part c). Next, a 6-F balloon catheter with a balloon diameter of 20 mm (Selecon balloon catheter; Clinical Supply, Gifu, Japan) was inserted through the right femoral vein or right internal jugular vein into the left adrenal vein and wedged in it. Left adrenal venography with 20 mL of iopamidol was performed with the balloon inflated, but the gastric varices were not completely opacified in any of the patients because of blood flow from the gastric varices into the dilated collateral veins, such as the inferior phrenic vein or pericardiacophrenic vein. We then inserted a 3-F microcatheter and performed selective catheterization of the gastric varices through a 6-F balloon catheter during balloon occlusion of the left adrenal vein. After insertion of the microcatheter into the gastric varices, it was flushed with contrast medium (iopamidol) to confirm that it filled the gastric varices and to measure the volume injected. The sclerosing agent, a mixture of 10% ethanolamine oleate (Odamin; Mochida Pharmaceutical, Tokyo, Japan) and the same dose of iopamidol, was injected slowly under fluoroscopic monitoring until the gastric fundal varices had been completely filled. A 20-mL volume of 50% glucose was injected through the microcatheter before injection of the sclerosing agent as a means of washing out any blood cells in the gastric varices (13). The maximum dose of the ethanolamine oleate/iopamidol mixture used at one time depended on the volume of gastric varices; however, in most patients, it was less than 20 mL. The ethanolamine oleate/iopamidol mixture remained in the varices for 15–17 hours (overnight) after injection with the occlusion balloon inflated. As much of the ethanolamine oleate/iopamidol mixture as possible was then withdrawn under fluoroscopic observation, and the procedure was terminated when a test injection of contrast medium (iopamidol) demonstrated that clots had formed in the varices. Blood pressure, pulse rate, electrocardiogram, arterial oxygen saturation (pulse oximeter), and urine volume were monitored throughout the proce-
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dure. Intravenous administration of 4,000 U of human haptoglobin (Green Cross, Osaka, Japan) during the procedure was used to prevent hemolysis and subsequent renal failure that may be induced by ethanolamine oleate (22). Follow-up Follow-up endoscopy and CT were performed at 1 week and 3 months after the balloon-occluded retrograde transvenous obliteration procedure and every 3 or 6 months thereafter, and hepatic function and blood cell counts were monitored monthly throughout the follow-up period. Technical success was defined by (i) complete clotting of the gastric varices as demonstrated by CT and (ii) disappearance of the gastric varices or reduced variceal size endoscopically.
RESULTS The Table summarizes the results of the balloon-occluded retrograde transvenous obliteration of gastric varices by the microcatheter insertion method. Left adrenal venography with 20 mL of iopamidol was performed with the balloon inflated, but the gastric varices were not opacified in any of the patients (Figure, part d). There were many large collateral veins, the inferior phrenic veins were observed in all patients, and the hemiazygos vein and/or pericardiacophrenic vein was observed in four patients. Selective catheterization of the gastric varices and subsequent venography were performed in all patients with the microcatheter without occlusion of the collateral veins (Figure, part e), and the gastric varices were filled with 8.5–28 mL of the ethanolamine oleate/ iopamidol mixture (Figure, part f). Technical success was achieved in one treatment session in all patients, and no major side effects were observed. All patients reported fever, and transient hemoglobinuria was observed during the procedure, but these symptoms had almost disappeared by the end of treatment. Hepatic function parameters did not change during or after the procedure. The serum amylase level of one patient was increased 1 week after the procedure, but it returned to within the normal range within 4 days after therapy. The length
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Figure. Gastric varices with collateral veins and a large gastrorenal shunt in a 71-year-old woman with bleeding gastric varices. (a) Endoscopic examination revealed huge gastric fundal varices with a red spot on the varices. (b) Contrast material– enhanced CT shows marked dilation of the gastric varices (arrows). (c) Celiac angiogram reveals marked dilation of the gastric varices (arrowheads), followed by a gastrorenal shunt (arrows), the left renal vein (LRV), splenic vein (SV), portal vein (PV), and inferior vena cava (IVC). (d) Left adrenal venography performed during 6-F balloon catheter occlusion (20 mm in diameter) shows the markedly dilated gastrorenal shunt (white arrowheads) and the inferior phrenic vein (arrow) and pericardiacophrenic veins (arrowhead), but no gastric varices are visible. (e) A 3-F microcatheter was inserted into the gastric varices through a 6-F balloon catheter wedged in the left adrenal vein. The arrow shows the tip of the microcatheter inserted into the gastric varices. Gastric variceal venography shows that the gastric varices are filled with contrast medium, but no collateral veins are seen. (f) Gastric varices are filled with the ethanolamine oleate/iopamidol mixture. (continues)
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ance of the varices 1 week after the procedure, but follow-up endoscopy 3 months after the procedure revealed disappearance of the gastric varices in seven of the patients and reduced variceal size in the other patient (Figure, part h). No recurrence or bleeding of gastric varices developed in any of the patients during the 3–36month follow-up period (mean, 13 months). Esophageal varices developed in four patients, and endoscopic variceal ligation was successful. One patient was found to have a hepatocellular carcinoma lesion 10 months after the procedure and was successfully treated with radiofrequency ablation therapy.
DISCUSSION
Figure. (continued) (g) One week after the procedure, contrast-enhanced CT shows that the gastric varices have been completely obliterated (arrows). (h) Follow-up endoscopy 3 months after the procedure reveals disappearance of the gastric varices.
of hospital stay ranged from 9 days to 20 days (mean, 14 days). The two patients who underwent the procedure for prevention had a shorter hospital stay (9 days each) than those with bleeding varices. One week after the procedure, contrast-enhanced CT showed gastric varices as areas of nonenhancement in all cases, meaning that clot formation had occurred (Figure, part g). There were no changes in the endoscopic appear-
Balloon-occluded retrograde transvenous obliteration has been used as a new radiologic modality for the treatment of gastric varices (1), and a very high initial success rate of obliteration of gastric varices has been reported (11–15). However, the technical success rate of the initial procedure was unsatisfactory, and two or more treatment sessions were often required to complete treatment (18,19), resulting in longer hospitalization. In the present study, we used a microcatheter insertion method in the procedure for balloon-occluded retrograde transvenous obliteration of gastric varices, and the results showed a very high initial success rate (100%) for obliteration of gastric varices in a single treatment session. As gastric varices progress, a gastrorenal shunt and/or collateral veins such as the inferior phrenic, hemiazygos, or pericardiacophrenic veins develop according to the degree of blood flow from the gastric varices, and occlusion of these collateral veins is essential to obliterate the gastric varices (14,18). Hirota et al (14) classified the degree of progression of gastric varices and collateral veins into five grades based on the adrenal venography findings during balloon occlusion: grade 1, no collateral veins; grade 2, small collateral veins; grade 3, a few collateral veins of medium to large size; grade 4, many large collateral veins; and grade 5, no occlusion of the left adrenal vein as a result of a very large gastrorenal shunt with rapid blood flow. Occlusion of the collateral
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veins is the essential first step in the treatment of patients with gastric varices of grade 3 or worse, and the investigators occluded these collateral veins with an injection of sclerosing agent or spring coils inserted through a microcatheter and selective catheterization (14). However, even when the collateral veins were occluded, the very large gastric varices could not be obliterated in a single treatment session through the occlusion balloon inflated in the adrenal vein, and second and third balloon-occluded retrograde transvenous obliteration procedures were often needed. In this study, we used a method of microcatheter insertion into gastric varices and found that the procedure was superior to the conventional approach. A balloon catheter was wedged in the adrenal vein, and the sclerosing agent was injected through the inflated balloon occlusion catheter. Advantages of our methods include (i) the fact that occlusion of collateral veins is not required to complete treatment and (ii) the use of a low dose of sclerosing agent. The first advantage is based on the fact that, despite the majority of our patients having Hirota (14) grade 4 gastric varices with many large collateral veins, it was easy to occlude the varices in one treatment session by the microcatheter insertion method without occluding the collateral veins. The technical success of the initial procedure by the microcatheter insertion method resulted in clearly shorter hospital stays (mean, 14 days) compared with the mean length of stay for conventional balloon-occluded retrograde transvenous obliteration of gastric varices (27 days) (15). The second advantage arises from the fact that the dose used for our selective obliteration of gastric varices (8.5–28 mL) was much lower than the 30 mL maximum dose of ethanolamine oleate/iopamidol mixture reported by Hirota et al (14), the 60 mL reported by Koito et al (12) and Sonomura et al (18), and the 62 mL reported by Akahane et al (13) for each session of conventional balloon-occluded retrograde transvenous obliteration of gastric varices. The lower dose may have reduced the complications associated with the procedure of balloon-occluded retrograde transvenous obliteration of gastric varices.
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Results of Balloon-occluded Retrograde Transvenous Obliteration of Gastric Varices by the Microcatheter Insertion Method Left Adrenal Venography Pt. No.
Endoscopic Classification*
Diameter of Gastrorenal Shunt (mm)
1† 2‡ 3‡ 4 5‡ 6 7‡ 8
Lg-cf Lg-f Lg-f Lg-cf Lg-f Lg-cf Lg-f Lg-cf
28 32 22 19 22 15 13 16
Collateral Veins IPV, IPV, IPV, IPV, IPV, IPV, IPV, IPV,
HAV PCV PCV HAV PCV, HAV HAV HAV HAV
Gastric Varices after Treatment
Dose of Ethanolamine Oleate (mL)
Endoscopy
CT
Follow-up (mo)
8.5 15 20 19 28 20 17.5 20
Reduced Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared
Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared Disappeared
36 18 26 5 7 4 3 3
Note.—HAV ⫽ hemiazygos vein; IPV ⫽ inferior phrenic vein; PCV ⫽ pericardiacophrenic vein. * See text for explanation (20, 21). † A hepatocellular carcinoma lesion was detected 10 months after the procedure and was successfully treated by radiofrequency ablation therapy. ‡ Esophageal varices were aggravated during the follow-up period, and successful endoscopic variceal ligation was performed.
Transjugular intrahepatic portosystemic shunts are commonly used to treat gastric varices, but 50% of fundic gastric varices fail to resolve after the procedure (7), and they may induce or aggravate hepatic encephalopathy (8 – 10). The balloon-occluded retrograde transvenous obliteration procedure, conversely, blocks gastric variceal blood flow with a very high success rate. Because gastrorenal shunts decrease portal venous pressure, their obliteration may cause portal venous pressure to increase and new collateral veins to the esophageal varices to develop, and four of our patients did in fact experience exacerbation of esophageal varices after balloon-occluded retrograde transvenous selective obliteration. Therefore, our procedure is likely to be a temporizing procedure for patients who are not candidates for a transjugular intrahepatic portosystemic shunt. We recommend it for patients who have progressive fundic gastric varices at risk of rupture and associated with a gastrorenal shunt or hepatic encephalopathy. In conclusion, balloon-occluded retrograde transvenous selective obliteration by the microcatheter insertion method is an effective treatment for progressive gastric varices with large collateral veins or a large gastrorenal shunt.
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