Dig Dis Sci (2014) 59:2325–2332 DOI 10.1007/s10620-014-3150-2
ORIGINAL ARTICLE
Efficacy of Transjugular Intrahepatic Portosystemic Shunt with Adjunctive Embolotherapy with Cyanoacrylate for Esophageal Variceal Bleeding Yongjun Shi • Xiangguo Tian • Jinhua Hu Junyong Zhang • Chunqing Zhang • Yongqing Yang • Chengyong Qin
•
Received: 1 January 2014 / Accepted: 30 March 2014 / Published online: 19 April 2014 Ó Springer Science+Business Media New York 2014
Abstract Background Transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive embolotherapy has recently been reported to be effective in the prevention of variceal hemorrhage of cirrhotic patients. However, further investigation of its long-term efficacy is still needed. Aim To examine the rebleeding, survival, and hepatic encephalopathy (HE) after treatment with TIPS alone and TIPS with adjunctive embolotherapy using cyanoacrylate for esophageal variceal bleeding. Methods Patients with refractory to endoscopic therapy for esophageal variceal bleeding were enrolled. TIPS was performed in 101 patients with adjunctive embolotherapy (n = 53) or alone (n = 48) between January 2006 and
Y. Shi X. Tian J. Hu J. Zhang C. Zhang C. Qin (&) Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan 250021, Shandong, People’s Republic of China e-mail: [email protected] Y. Shi e-mail: [email protected] X. Tian e-mail: [email protected] J. Hu e-mail: [email protected] J. Zhang e-mail: [email protected] C. Zhang e-mail: [email protected] Y. Yang Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan 250013, Shandong, People’s Republic of China e-mail: [email protected]
December 2011. Chart reviews were performed to determine rebleeding, survival rates, and the incidence of HE. Results Recurrent hemorrhage occurred in 12 (11.9 %) patients during the mean follow-up periods of 35.8 months. Rebleeding was observed in 9/48 (18.8 %) patients in TIPS alone group and 3/53 (5.7 %) patients in TIPS with adjunctive embolotherapy group (p = 0.042). Death occurred in 30 patients during follow-up (TIPS alone: n = 16, TIPS with adjunctive embolotherapy: n = 14, p = 0.447). Twenty-six episodes of HE occurred in 18 patients in TIPS alone group and 16 episodes occurred in 10 patients in TIPS with embolotherapy group. The probability of HE was significantly higher in TIPS alone group than in TIPS with embolotherapy group (p = 0.019). Conclusions TIPS with adjunctive embolotherapy with cyanoacrylate is relatively safe and effective, with a lower rebleeding and HE incidence in comparison of TIPS alone. Keywords Transjugular intrahepatic portosystemic shunt (TIPS) Variceal bleeding Embolotherapy Cyanoacrylate
Introduction According to current guidelines, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as the rescue therapy after failure of combined medical and endoscopic therapies for prevention of variceal hemorrhage [1, 2]. In an attempt to improve the patency of this technique, covered stents were introduced. These stents have been in use for more than a decade now, and the results in large cohort and comparative studies clearly demonstrate their superiority over bare stents [3–6]. Although the long-term patency rate has improved since the advent of coated
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stents, hepatic encephalopathy (HE) remains a complication of TIPS, and rebleeding after TIPS is still needing improved. Recently, combination of variceal embolotherapy during TIPS creation has been described by some reports [7, 8]. However, there have been few reports directly comparing combination of variceal embolotherapy during TIPS versus TIPS alone in terms of clinical outcomes [9, 10]. Tesdal et al. [9] reported that TIPS and adjunctive embolotherapy of gastroesophageal collateral vessels significantly lower the rebleeding rate in comparison with TIPS alone. But Xiao et al. [10] reported TIPS with embolotherapy cannot reduce the risk of rebleeding if portal pressure gradient (PPG) is less than 12 mm Hg after TIPS. So, the results were not the same, and most of the control trial was bare stent for TIPS and coil for embolotherapy. In this retrospective study, adjunctive embolization of esophageal varices and their feeding veins was performed with cyanoacrylate during the TIPS procedure, and the polytetrafluoroethylene (PTFE)-covered stent was used for TIPS. To evaluate the efficacy of TIPS combined with esophageal variceal embolization, outcomes in patients treated with TIPS combined with embolization of esophageal varices were compared with those in patients treated with TIPS alone.
Methods Patients Between January 2006 and December 2011, a total of 101 patients in whom the TIPS procedure or TIPS combined with embolization had been successfully performed in our hospital were included in this retrospective study. Inclusion criteria included the following: age [18 years, known hepatic cirrhosis based on findings of histological or typical cross-sectional imaging (ultrasound, computed tomography, or magnetic resonance imaging), and acute (within 24 h) or recent ([24 h prior) hemorrhage from esophageal varices refractory to endoscopic therapy (sclerotherapy or ligation). Exclusion criteria were as follows: concomitant liver cancer or other cancers, concomitant widespread portal vein embolism, grade II or higher hepatic encephalopathy, obvious jaundice with total bilirubin levels three times higher than normal, obvious bleeding tendency with a prothrombin time [25 s, severe hypertension, coronary heart disease, or cardiopulmonary insufficiency. Of the 101 patients, 53 of them received TIPS combined with embolization and 48 received TIPS alone. PTFE-covered stent was deployed in TIPS creation. Although the patients with large supplying veins were strongly recommended to receive the TIPS combined embolotherapy with
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Dig Dis Sci (2014) 59:2325–2332 Table 1 Clinical characteristics of patients in the 2 study groups TIPS ? EMB (n = 53)
TIPS (n = 48)
p
0.325
Sex (F/M) Female
15
18
Male
38
30
51.0 ± 11.0
49.7 ± 9.0
Hepatitis B/C
37
34
Alcohol Other
12 4
13 1
A
16
11
B
29
28
C
8
9
36.2 ± 17.5
35.4 ± 18.7
Age (years) Etiology of cirrhosis
0.422
Child–Pugh classification
Duration of follow-up (months)
0.536
0.685
0.963
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
cyanoacrylate, the choice of the treatment was based on the intentions of the patients or their family members after being given a sufficient explanation of the two treatment methods, including the complications, prognosis, and cost. A chart review of all the patients was performed. Demographic and clinical information such as type of underlying liver disease, results of liver function tests, and renal function prior to and after the procedures was recorded. The clinical characteristics of patients in the two study groups are shown in Table 1. No statistically significant differences were identified between the study groups. The mean follow-up period was 35.4 months in the TIPS alone group and 36.2 months in the TIPS ? embolization group. This study was approved by the local ethics committee, and informed written consent was obtained from each patient. TIPS Procedure The TIPS procedure has been described previously [11]. After puncturing the right internal jugular vein, a 10-F, 41-cm-long sheath was placed in the suprahepatic portion of the inferior vena cava. After catheterization of the right hepatic vein, the measure of hepatic venous pressure and the portal puncture were performed. With the use of a hydrophilic guide wire, the portal vein was catheterized. The portal pressure was measured while the portography was performed. The dilation of the intrahepatic parenchymal tract was performed using a low-profile balloon with 8 mm diameter. Fluency stent grafts (8–10 mm 9 6 cm) were
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Fig. 1 Procedures of transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive embolotherapy in 63-year-old male with alcoholic liver cirrhosis. a A 5-F Cobra catheter was inserted into splenic vein, and splenoportography was carried out to assess the varices and the afferent veins. b The left gastric vein was then selected for venography to evaluate the size of varices, blood flow
velocity, and the amount of contrast medium needed to fill the varices. c Cyanoacrylate was injected into the low esophageal varices and into the vessels in the vicinity of the gastric cardia and fundus via the left gastric vein and its anterior and posterior branches. d After covered stent was inserted and dilated, splenoportography showed that portal– azygos collaterals were completely occluded, and the stent was patent
deployed. The Fluency stent graft is a PTFE-encapsulated grid-like cylinder made of a biocompatible nickel–titanium alloy. The length of the uncovered portion is approximately 2.7 mm at each end. In order to diminish the influence on the hepatic inflow of the portal vein and the shunt caused by the PTFE-covered stent as much as possible, the portion of the covered stent inside the portal vein should be as short as possible, and the other side of the stent should be deployed near the junction part of the hepatic veins and the inferior vena cava. The portography was performed where the portal pressure and hepatic venous pressure were measured after the placement of stents. The stent for TIPS was dilated to 8 or 10 mm according to the portal pressure gradient (less than 12 mmHg).
In the combination group, cyanoacrylate embolization of gastroesophageal varices was performed before stent insertion (Fig. 1). The main feeding vessel (e.g., the left, short, or posterior gastric veins) was selected, and a 5-F cobra catheter or microcatheter was used for injection of cyanoacrylate into all the varices in the lower esophagus and gastric fundus and into all the feeding vessels. Portal vein venography was then performed after the embolization. If other feeding vessels were detected, the above procedure was repeated until blood flow in the varices ceased completely. After embolization, stent placement was conducted as above methods. After final measurement of portal pressure, completion shunt venography was performed.
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Follow-Up All patients were informed of the purpose of this study and asked to enroll in the follow-up protocol. Evaluations were performed monthly after discharge for 3 months and again every 3 months thereafter. At each visit, the medical history was briefly reviewed to record possible gastrointestinal bleeding, alcohol intake, concurrent medications, and patient complaints. In addition, brief physical examination was performed including estimation of ascites, and HE was detected by routine neurological examination and laboratory profiling. The condition of the TIPS tract was determined using color Doppler sonography every 3–6 months. The hemodynamic changes, including the velocity of the portal vein and intrahepatic shunt, were monitored. Endoscopy was performed every 6–12 months to evaluate esophageal varices. Statistical Analysis All results were expressed as either mean ± SD or percentages. Quantitative variables were compared using twosample Student’s t tests, and qualitative variables were compared using either Fisher’s exact test or the chi-squared test (with Yates correction) wherever appropriate. Kaplan– Meier analysis was used to evaluate variceal rebleeding, survival, and the incidence of HE. Comparisons were carried out using the log-rank test. p values B0.05 were considered to be significant. Statistical computation was performed using SPSS 17.0 software.
Dig Dis Sci (2014) 59:2325–2332 Table 2 Pre- and post-TIPS portosystemic pressure gradient among groups
Before TIPS After TIPS
TIPS ? EMB (n = 53)
TIPS (n = 48)
15.2 ± 2.8
16.6 ± 5.0
6.7 ± 2.7
7.7 ± 3.1
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization. Values are mean ± SD
Stent patency was evaluated on color Doppler ultrasonography. Shunt stenosis or occlusion occurred in 20 (19.8 %) patients (8 in the TIPS group and 12 in the TIPS ? embolization group; p = 0.452) during the mean follow-up time of 35.8 months. Recanalization with balloon angioplasty or insertion of a new stent was successful in 17 of these patients. In the remaining three patients failed in recanalization, one was in the TIPS alone group and two were in the TIPS ? embolization group. The patient in the TIPS alone group died of uncontrolled rebleeding. The remaining 2 patients in the TIPS ? embolization group received surgery. Cyanoacrylate embolization was performed in 53 patients prior to TIPS insertion. The varices and their feeding vessels, including the lower esophageal and periesophageal varices and/or the cardial submucosal and perforating vessels, were sufficiently obliterated with cyanoacrylate in all 53 patients. No contrast flow was seen at the time of completion of TIPS venography following embolization in any of the cases. The mean volume of cyanoacrylate used per patient was 7.5 mL. Rebleeding
Results Technique Results TIPS insertion was technically successful in all 101 patients. Hemodynamic success was also achieved in all patients. A single-coated stent graft was utilized for TIPS in 87 patients, and double-coated stent grafts were used in 14 patients. Insertion of 10-mm-diameter stents was successful in 53 patients, while 8-mm-diameter stents were placed in 48 patients. The median initial portosystemic gradient was 15.8 mmHg (range 10–31.5 mmHg), and the final portosystemic gradient was 7.2 mmHg (range 2–16 mmHg). No statistically significant differences in the median initial (16.6 ± 5.0 vs. 15.2 ± 2.8 mmHg, p = 0.092) and final (6.8 ± 3.2 vs. 6.4 ± 2.6 mmHg, p = 0.097) portosystemic pressure gradients were observed between patients in the TIPS alone and TIPS ? embolization groups (Table 2). No immediate procedure-related complications developed.
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Following TIPS insertion, recurrent hemorrhage occurred in 12 (11.9 %) patients during the median clinical followup time period: 9/48 (18.6 %) in the TIPS alone group and 3/53 (5.7 %) in the TIPS ? embolization group (Table 3, p = 0.042). The cumulative probability of the absence of rebleeding in all the patients after 1, 3, and 5 years was 96.0, 89.7, and 83.2 %, respectively. In the TIPS group, the probability of the absence of rebleeding at 1, 3, and 5 years was 93.6, 80.9, and 75.9 %, respectively, whereas that in the TIPS ? embolization group was 98.1, 94.3, and 89.8 %, respectively (Fig. 2, p = 0.048). Recurrent variceal hemorrhage was observed in seven patients (Table 3). Subgroup analysis of rebleeding comparing patients by type of varices showed recurrent hemorrhage in two patients (28.5 %) with gastric varices (all in the TIPS alone group) and five patients (71.5 %) with esophageal varices (one in the nonembolization group and four in the embolization group). In the TIPS alone group, of the six patients with variceal rebleeding, two patients died of
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Table 3 Post-TIPS rebleeding, HE, and survival TIPS ? EMB (n = 53) Rebleeding (n)
3
TIPS (n = 48) 9
p
0.042
From and cause Variceal rebleeding
1
6
0.029
Esophageal varices
1
4
0.126
Gastric varices Nonvariceal bleeding Esophageal/gastric ulcer PHG
0
2
0.082
2
3
0.566
2 0
1 2
0.613 0.082
HE (n)
10
18
0.037
Death (n)
14
16
0.447
Causes of death Variceal bleeding
0
2
0.082
Progressive liver failure
9
10
0.621
HCC
2
1
0.613
Sepsis
1
1
0.944
Peritonitis
2
1
0.613
Cerebral vascular accident
0
1
0.221
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, PHG portal hypertensive gastropathy, HE hepatic encephalopathy, HCC hepatocellular carcinoma
Fig. 3 Kaplan–Meier estimation of survival among all patients undergoing TIPS with adjunctive embolotherapy versus TIPS alone (p = 0.466). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
Survival Death occurred in 30 patients during the follow-up period, including 16 patients in the TIPS alone group and 14 patients in the TIPS ? embolization group (p = 0.447). Kaplan– Meier estimation of cumulative survival for all patients after 1, 3, and 5 years was 95, 77.1, and 53.9 %, respectively. The corresponding cumulative survival rate after 1, 3, and 5 years was 88.8, 71.8, and 49.6 %, respectively, in the TIPS alone group and 94.3, 82.1, and 57.3 %, respectively, in the TIPS ? embolization group (Fig. 3). No statistically significant difference was noted between the 2 groups in terms of survival (p = 0.466). As shown in Table 3, liver dysfunction was the main etiologies. Mortality due to rebleeding occurred in 2.9 % (3 of 101 patients) during follow-up. No death due to variceal rebleeding occurred in the embolization group. HE
Fig. 2 Kaplan–Meier estimation of the probability of rebleeding among all patients in whom TIPS with adjunctive embolotherapy was performed versus TIPS alone (p = 0.048). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
uncontrolled rebleeding. Further variceal embolization was required for three patients after rebleeding. For the remaining patients, endoscopic variceal ligation (n = 1) was performed.
During follow-up, 26 episodes of HE occurred in 18 patients (37.5 %) in the TIPS alone group and 16 episodes occurred in 10 patients (18.9 %) in the TIPS ? embolization group (p = 0.037). The probability of the absence of encephalopathy in the TIPS versus TIPS ? embolization groups was 91.7 % versus 96.2 % at 1 month, 78.1 % versus 92.5 % at 6 months, 70.8 % versus 88.5 % at 1 year, 62.6 % versus 81.1 % at 2 years, and 53.3 % versus 76.1 % at 5 years. The actuarial curves of the probability of HE were significantly higher in the TIPS alone group than in the TIPS ? embolization group (p = 0.019, Fig. 4). Most encephalopathic episodes were mild and responded well to medical therapy.
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Dig Dis Sci (2014) 59:2325–2332 Table 4 Complications of the procedures TIPS ? EMB (n = 53)
TIPS (n = 48)
p
28
23
0.622
SBP
4
5
0.613
Hepatic myelopathy
1
1
0.944
Fever
26
19
0.339
Abdominal pain
Total complications
22
16
0.397
Bacteremia
4
3
0.797
Ulcer
0
1
0.221
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, SBP spontaneous bacterial peritonitis
Fig. 4 Kaplan–Meier estimation of the probability of HE among all patients in whom TIPS with adjunctive embolotherapy was performed versus TIPS alone (p = 0.019). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, HE hepatic encephalopathy
Reduction in shunt diameter was required in 10 of 28 patients with recurrent, spontaneous encephalopathy. HE improved in all the patients after shunt diameter reduction. Complications Complications of the two procedures examined in this study are shown in Table 4. In total, 28 patients in the TIPS ? embolization group and 23 patients in the TIPS group experienced complications (p = 0.622). Spontaneous bacterial peritonitis developed in five patients in the TIPS alone group and 4 patients in the TIPS ? embolization group (p = 0.613). In addition, hepatic myelopathy developed in 1 patient in each group (p = 0.944), and both these patients received liver transplantation. As shown in Table 4, no significant inter-group differences were observed in the number of patients with other complications.
Discussion Since its introduction in the 1980s [12], the TIPS procedure has played a major role in the management of portal hypertension. In 2004, the polytetrafluoroethylene-covered Viatorr stent graft was approved by the U.S. Food and Drug Administration. This device improves shunt patency by minimizing transmural bile permeation and thereby reducing tissue ingrowth. Although the long-term patency rate has improved with the use of coated stents, the incidence of HE associated with TIPS is still a problem [13– 15].
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Variceal embolization therapy has been studied before the advent of TIPS. Lunderquist et al. [16] described percutaneous transhepatic obliteration for gastroesophageal varices in 1974. However, it has not attained widespread clinical acceptance because of the higher rebleeding rate associated with this approach [17–20]. Percutaneous transhepatic variceal embolization (PTVE) with cyanoacrylate is a modified procedure for conventional percutaneous transhepatic obliteration. With this technique, both the varices and their feeding vessels are sufficiently and permanently obliterated by cyanoacrylate. This modified PTVE technique has been confirmed as an effective and safe method for preventing variceal rebleeding [21, 22]. However, PTVE did not alleviate portal hypertension; therefore, rebleeding still occurred in approximately 20.6–46.1 % in patients in whom cyanoacrylate had not permeated the lower esophageal varices [22]. To improve the long-term results of TIPS, combination of variceal embolotherapy during TIPS creation has been described by many reports [7, 8]. Up to now, in most control trial, the bare stent was used for TIPS, and coil was used for adjunctive embolotherapy. And the results of these studies were contradictory. However, some studies argue that TIPS creation alone is sufficient to manage variceal gastrointestinal hemorrhage in most instances [23, 24]. To our knowledge, there is no published data evaluating the variceal embolotherapy with cyanoacrylate combined with TIPS versus TIPS creation alone. The purpose of this retrospective–prospective study was to compare the rebleeding rate, survival, and hepatic encephalopathy between patients treated with the two different procedures. Variceal embolotherapy with cyanoacrylate combined with TIPS insertion may be rational approach for variceal rebleeding. The combination of these two principal techniques not only decreases the portosystemic pressure gradient but also occludes the gastroesophageal varices and their feeding veins. In the present study, all patients suffering from gastroesophageal variceal hemorrhage were
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successfully treated with TIPS alone or with variceal cyanoacrylate embolization combined with TIPS. The overall post-operative rebleeding rate was 11.9 % (12/101), but the long-term rebleeding rate in the patients treated with TIPS combined with variceal embolization was only 5.7 % (3/ 53), compared with 18.8 % (9/48) in the patients treated using TIPS alone. Thus, the rebleeding rate in the patients receiving TIPS combined with cyanoacrylate embolization was significantly lower than that in the patients treated with TIPS alone. This result may be attributed to the extensive and permanent obliteration achieved using variceal cyanoacrylate embolotherapy. Occlusion of all lower esophageal and peri- or para-esophageal varices, the submucosal varices, and the adventitial plexus of the cardia and fundus is possible using this technique. Previous reports showed that the relapse rate in patients who underwent adequate embolization of the feeding vessel to the varices was significantly lower than the rate in those with inadequate embolization [25]. Furthermore, the decreased PPG after shunts may also prevent the recanalization of the obliterated varices. The data from our results also support the findings of Tesdal et al. [9]. Although bare stent was used in their study, they embolized both the proximal and the peripheral level of the collateral vessels using long-acting occluding agents such as the combination of liquid and mechanical materials. They think that if the collateral vessels had been only placed some coils at the proximal level, it would hardly prevent the filling of distal feeder vessels and their varices. HE is a common complication after TIPS. Although most patients respond well to conservative medical therapy (i.e., restriction of dietary protein, nonabsorbable disaccharides, and nonabsorbable antibiotics), about 3–7 % of the patients treated with TIPS tend to experience recurrent or refractory encephalopathy necessitating shunt occlusion or reduction [26]. Thus, HE in cirrhotic patients following the placement of TIPS stents is still a severe problem impeding the improvement in this procedure. In this study, HE developed in 18 patients (37.5 %) in the TIPS group, but in only 10 (18.9 %) patients in the TIPS ? embolization group. This difference was statistically significant. The lower recurrence of HE in the adjunctive group may have resulted from the complete obliteration of the portosystemic shunts (the varices and their feeding veins). Furthermore, to some degree, the incidence of HE is related to the shunt diameter. In the adjunctive group, the obliteration of the varices allows for the use of smaller stent in the TIPS procedure, which also reduces the HE incidence. In terms of procedural skills, some points should be mentioned. First, embolization of gastroesophageal varices must be performed prior to stent insertion in order to achieve adequate and extensive obliteration of the lower
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esophageal varices and their feeding veins and to avoid introduction of cyanoacrylate into the systemic circulation. Before variceal embolotherapy, splenoportography is performed to assess the varices and the afferent veins. Then, the left gastric vein is selected for venography to determine the size of the esophageal varices, blood flow velocity, and the amount of contrast medium needed to fill the varices as well as the injection method and required quantities of cyanoacrylate. Second, cyanoacrylate must be injected slowly and continuously so that the cyanoacrylate is completely deposited around the gastroesophageal varices. Once the cyanoacrylate has been deposited in the gastric coronary vein, injection must stop immediately to prevent flow reflux and avoid introduction of cyanoacrylate into the systemic circulation. In conclusion, our results indicated that in patients with gastroesophageal variceal bleeding, TIPS combined with embolization of varices can decrease the rebleeding and HE rates compared with TIPS alone, although no survival benefit was observed. Despite the value of this finding, several important limitations of this study must be noted. First, this study was mainly retrospective and the sample was not randomized. Second, the investigation was conducted at a single hospital with a sample limited in size. A prospective, controlled trial comparing these 2 interventions is warranted to determine the optimal management.
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gastroesophageal varices: results in 400 patients. Am J Roentgenol. 1989;152:755–760. Smith-Laing G, Scott J, Long RG, Dick R, Sherlock S. Role of percutaneous transhepatic obliteration of varices in the management of hemorrhage from gastroesophageal varices. Gastroenterology. 1981;80:1031–1036. Scott J, Dick R, Long RG, Sherlock S. Percutaneous transhepatic obliteration of gastro-oesophageal varices. Lancet. 1976;2:53–55. Uflacker R. Percutaneous transhepatic obliteration of gastroesophageal varices using absolute alcohol. Radiology. 1983;146:621–625. Zhang CQ, Liu FL, Liang B, et al. A modified percutaneous transhepatic variceal embolization with 2-octyl cyanoacrylate versus endoscopic ligation in esophageal variceal bleeding management: randomized controlled trial. Dig Dis Sci. 2008;53:2258–2267. Zhang CQ, Liu FL, Liang B, et al. A modified percutaneous transhepatic varices embolization with 2-octyl cyanoacrylate in the treatment of bleeding esophageal varices. J Clin Gastroenterol. 2009;43:463–469. Martin M, Zajko AB, Orons PD, et al. Transjugular intrahepatic portosystemic shunt in the management of variceal bleeding: indications and clinical results. Surgery. 1993;114:719–726. Haskal ZJ, Scott M, Rubin RA, Cope C. Intestinal varices: treatment with the transjugular intrahepatic portosystemic shunt. Radiology. 1994;191:183–187. Takase Y, Shibuya S, Chikamori F, Orii K, Iwasaki Y. Recurrence factors studied by percutaneous transhepatic portography before and after endoscopic sclerotherapy for esophageal varices. Hepatology. 1990;11:348–352. Luca A, D’Amico G, La Galla R, Midiri M, Morabito A, Pagliaro L. TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized clinical trials. Radiology. 1999;212:411–421.
ORIGINAL ARTICLE
Efficacy of Transjugular Intrahepatic Portosystemic Shunt with Adjunctive Embolotherapy with Cyanoacrylate for Esophageal Variceal Bleeding Yongjun Shi • Xiangguo Tian • Jinhua Hu Junyong Zhang • Chunqing Zhang • Yongqing Yang • Chengyong Qin
•
Received: 1 January 2014 / Accepted: 30 March 2014 / Published online: 19 April 2014 Ó Springer Science+Business Media New York 2014
Abstract Background Transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive embolotherapy has recently been reported to be effective in the prevention of variceal hemorrhage of cirrhotic patients. However, further investigation of its long-term efficacy is still needed. Aim To examine the rebleeding, survival, and hepatic encephalopathy (HE) after treatment with TIPS alone and TIPS with adjunctive embolotherapy using cyanoacrylate for esophageal variceal bleeding. Methods Patients with refractory to endoscopic therapy for esophageal variceal bleeding were enrolled. TIPS was performed in 101 patients with adjunctive embolotherapy (n = 53) or alone (n = 48) between January 2006 and
Y. Shi X. Tian J. Hu J. Zhang C. Zhang C. Qin (&) Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan 250021, Shandong, People’s Republic of China e-mail: [email protected] Y. Shi e-mail: [email protected] X. Tian e-mail: [email protected] J. Hu e-mail: [email protected] J. Zhang e-mail: [email protected] C. Zhang e-mail: [email protected] Y. Yang Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan 250013, Shandong, People’s Republic of China e-mail: [email protected]
December 2011. Chart reviews were performed to determine rebleeding, survival rates, and the incidence of HE. Results Recurrent hemorrhage occurred in 12 (11.9 %) patients during the mean follow-up periods of 35.8 months. Rebleeding was observed in 9/48 (18.8 %) patients in TIPS alone group and 3/53 (5.7 %) patients in TIPS with adjunctive embolotherapy group (p = 0.042). Death occurred in 30 patients during follow-up (TIPS alone: n = 16, TIPS with adjunctive embolotherapy: n = 14, p = 0.447). Twenty-six episodes of HE occurred in 18 patients in TIPS alone group and 16 episodes occurred in 10 patients in TIPS with embolotherapy group. The probability of HE was significantly higher in TIPS alone group than in TIPS with embolotherapy group (p = 0.019). Conclusions TIPS with adjunctive embolotherapy with cyanoacrylate is relatively safe and effective, with a lower rebleeding and HE incidence in comparison of TIPS alone. Keywords Transjugular intrahepatic portosystemic shunt (TIPS) Variceal bleeding Embolotherapy Cyanoacrylate
Introduction According to current guidelines, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as the rescue therapy after failure of combined medical and endoscopic therapies for prevention of variceal hemorrhage [1, 2]. In an attempt to improve the patency of this technique, covered stents were introduced. These stents have been in use for more than a decade now, and the results in large cohort and comparative studies clearly demonstrate their superiority over bare stents [3–6]. Although the long-term patency rate has improved since the advent of coated
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stents, hepatic encephalopathy (HE) remains a complication of TIPS, and rebleeding after TIPS is still needing improved. Recently, combination of variceal embolotherapy during TIPS creation has been described by some reports [7, 8]. However, there have been few reports directly comparing combination of variceal embolotherapy during TIPS versus TIPS alone in terms of clinical outcomes [9, 10]. Tesdal et al. [9] reported that TIPS and adjunctive embolotherapy of gastroesophageal collateral vessels significantly lower the rebleeding rate in comparison with TIPS alone. But Xiao et al. [10] reported TIPS with embolotherapy cannot reduce the risk of rebleeding if portal pressure gradient (PPG) is less than 12 mm Hg after TIPS. So, the results were not the same, and most of the control trial was bare stent for TIPS and coil for embolotherapy. In this retrospective study, adjunctive embolization of esophageal varices and their feeding veins was performed with cyanoacrylate during the TIPS procedure, and the polytetrafluoroethylene (PTFE)-covered stent was used for TIPS. To evaluate the efficacy of TIPS combined with esophageal variceal embolization, outcomes in patients treated with TIPS combined with embolization of esophageal varices were compared with those in patients treated with TIPS alone.
Methods Patients Between January 2006 and December 2011, a total of 101 patients in whom the TIPS procedure or TIPS combined with embolization had been successfully performed in our hospital were included in this retrospective study. Inclusion criteria included the following: age [18 years, known hepatic cirrhosis based on findings of histological or typical cross-sectional imaging (ultrasound, computed tomography, or magnetic resonance imaging), and acute (within 24 h) or recent ([24 h prior) hemorrhage from esophageal varices refractory to endoscopic therapy (sclerotherapy or ligation). Exclusion criteria were as follows: concomitant liver cancer or other cancers, concomitant widespread portal vein embolism, grade II or higher hepatic encephalopathy, obvious jaundice with total bilirubin levels three times higher than normal, obvious bleeding tendency with a prothrombin time [25 s, severe hypertension, coronary heart disease, or cardiopulmonary insufficiency. Of the 101 patients, 53 of them received TIPS combined with embolization and 48 received TIPS alone. PTFE-covered stent was deployed in TIPS creation. Although the patients with large supplying veins were strongly recommended to receive the TIPS combined embolotherapy with
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Dig Dis Sci (2014) 59:2325–2332 Table 1 Clinical characteristics of patients in the 2 study groups TIPS ? EMB (n = 53)
TIPS (n = 48)
p
0.325
Sex (F/M) Female
15
18
Male
38
30
51.0 ± 11.0
49.7 ± 9.0
Hepatitis B/C
37
34
Alcohol Other
12 4
13 1
A
16
11
B
29
28
C
8
9
36.2 ± 17.5
35.4 ± 18.7
Age (years) Etiology of cirrhosis
0.422
Child–Pugh classification
Duration of follow-up (months)
0.536
0.685
0.963
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
cyanoacrylate, the choice of the treatment was based on the intentions of the patients or their family members after being given a sufficient explanation of the two treatment methods, including the complications, prognosis, and cost. A chart review of all the patients was performed. Demographic and clinical information such as type of underlying liver disease, results of liver function tests, and renal function prior to and after the procedures was recorded. The clinical characteristics of patients in the two study groups are shown in Table 1. No statistically significant differences were identified between the study groups. The mean follow-up period was 35.4 months in the TIPS alone group and 36.2 months in the TIPS ? embolization group. This study was approved by the local ethics committee, and informed written consent was obtained from each patient. TIPS Procedure The TIPS procedure has been described previously [11]. After puncturing the right internal jugular vein, a 10-F, 41-cm-long sheath was placed in the suprahepatic portion of the inferior vena cava. After catheterization of the right hepatic vein, the measure of hepatic venous pressure and the portal puncture were performed. With the use of a hydrophilic guide wire, the portal vein was catheterized. The portal pressure was measured while the portography was performed. The dilation of the intrahepatic parenchymal tract was performed using a low-profile balloon with 8 mm diameter. Fluency stent grafts (8–10 mm 9 6 cm) were
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Fig. 1 Procedures of transjugular intrahepatic portosystemic shunt (TIPS) with adjunctive embolotherapy in 63-year-old male with alcoholic liver cirrhosis. a A 5-F Cobra catheter was inserted into splenic vein, and splenoportography was carried out to assess the varices and the afferent veins. b The left gastric vein was then selected for venography to evaluate the size of varices, blood flow
velocity, and the amount of contrast medium needed to fill the varices. c Cyanoacrylate was injected into the low esophageal varices and into the vessels in the vicinity of the gastric cardia and fundus via the left gastric vein and its anterior and posterior branches. d After covered stent was inserted and dilated, splenoportography showed that portal– azygos collaterals were completely occluded, and the stent was patent
deployed. The Fluency stent graft is a PTFE-encapsulated grid-like cylinder made of a biocompatible nickel–titanium alloy. The length of the uncovered portion is approximately 2.7 mm at each end. In order to diminish the influence on the hepatic inflow of the portal vein and the shunt caused by the PTFE-covered stent as much as possible, the portion of the covered stent inside the portal vein should be as short as possible, and the other side of the stent should be deployed near the junction part of the hepatic veins and the inferior vena cava. The portography was performed where the portal pressure and hepatic venous pressure were measured after the placement of stents. The stent for TIPS was dilated to 8 or 10 mm according to the portal pressure gradient (less than 12 mmHg).
In the combination group, cyanoacrylate embolization of gastroesophageal varices was performed before stent insertion (Fig. 1). The main feeding vessel (e.g., the left, short, or posterior gastric veins) was selected, and a 5-F cobra catheter or microcatheter was used for injection of cyanoacrylate into all the varices in the lower esophagus and gastric fundus and into all the feeding vessels. Portal vein venography was then performed after the embolization. If other feeding vessels were detected, the above procedure was repeated until blood flow in the varices ceased completely. After embolization, stent placement was conducted as above methods. After final measurement of portal pressure, completion shunt venography was performed.
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Follow-Up All patients were informed of the purpose of this study and asked to enroll in the follow-up protocol. Evaluations were performed monthly after discharge for 3 months and again every 3 months thereafter. At each visit, the medical history was briefly reviewed to record possible gastrointestinal bleeding, alcohol intake, concurrent medications, and patient complaints. In addition, brief physical examination was performed including estimation of ascites, and HE was detected by routine neurological examination and laboratory profiling. The condition of the TIPS tract was determined using color Doppler sonography every 3–6 months. The hemodynamic changes, including the velocity of the portal vein and intrahepatic shunt, were monitored. Endoscopy was performed every 6–12 months to evaluate esophageal varices. Statistical Analysis All results were expressed as either mean ± SD or percentages. Quantitative variables were compared using twosample Student’s t tests, and qualitative variables were compared using either Fisher’s exact test or the chi-squared test (with Yates correction) wherever appropriate. Kaplan– Meier analysis was used to evaluate variceal rebleeding, survival, and the incidence of HE. Comparisons were carried out using the log-rank test. p values B0.05 were considered to be significant. Statistical computation was performed using SPSS 17.0 software.
Dig Dis Sci (2014) 59:2325–2332 Table 2 Pre- and post-TIPS portosystemic pressure gradient among groups
Before TIPS After TIPS
TIPS ? EMB (n = 53)
TIPS (n = 48)
15.2 ± 2.8
16.6 ± 5.0
6.7 ± 2.7
7.7 ± 3.1
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization. Values are mean ± SD
Stent patency was evaluated on color Doppler ultrasonography. Shunt stenosis or occlusion occurred in 20 (19.8 %) patients (8 in the TIPS group and 12 in the TIPS ? embolization group; p = 0.452) during the mean follow-up time of 35.8 months. Recanalization with balloon angioplasty or insertion of a new stent was successful in 17 of these patients. In the remaining three patients failed in recanalization, one was in the TIPS alone group and two were in the TIPS ? embolization group. The patient in the TIPS alone group died of uncontrolled rebleeding. The remaining 2 patients in the TIPS ? embolization group received surgery. Cyanoacrylate embolization was performed in 53 patients prior to TIPS insertion. The varices and their feeding vessels, including the lower esophageal and periesophageal varices and/or the cardial submucosal and perforating vessels, were sufficiently obliterated with cyanoacrylate in all 53 patients. No contrast flow was seen at the time of completion of TIPS venography following embolization in any of the cases. The mean volume of cyanoacrylate used per patient was 7.5 mL. Rebleeding
Results Technique Results TIPS insertion was technically successful in all 101 patients. Hemodynamic success was also achieved in all patients. A single-coated stent graft was utilized for TIPS in 87 patients, and double-coated stent grafts were used in 14 patients. Insertion of 10-mm-diameter stents was successful in 53 patients, while 8-mm-diameter stents were placed in 48 patients. The median initial portosystemic gradient was 15.8 mmHg (range 10–31.5 mmHg), and the final portosystemic gradient was 7.2 mmHg (range 2–16 mmHg). No statistically significant differences in the median initial (16.6 ± 5.0 vs. 15.2 ± 2.8 mmHg, p = 0.092) and final (6.8 ± 3.2 vs. 6.4 ± 2.6 mmHg, p = 0.097) portosystemic pressure gradients were observed between patients in the TIPS alone and TIPS ? embolization groups (Table 2). No immediate procedure-related complications developed.
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Following TIPS insertion, recurrent hemorrhage occurred in 12 (11.9 %) patients during the median clinical followup time period: 9/48 (18.6 %) in the TIPS alone group and 3/53 (5.7 %) in the TIPS ? embolization group (Table 3, p = 0.042). The cumulative probability of the absence of rebleeding in all the patients after 1, 3, and 5 years was 96.0, 89.7, and 83.2 %, respectively. In the TIPS group, the probability of the absence of rebleeding at 1, 3, and 5 years was 93.6, 80.9, and 75.9 %, respectively, whereas that in the TIPS ? embolization group was 98.1, 94.3, and 89.8 %, respectively (Fig. 2, p = 0.048). Recurrent variceal hemorrhage was observed in seven patients (Table 3). Subgroup analysis of rebleeding comparing patients by type of varices showed recurrent hemorrhage in two patients (28.5 %) with gastric varices (all in the TIPS alone group) and five patients (71.5 %) with esophageal varices (one in the nonembolization group and four in the embolization group). In the TIPS alone group, of the six patients with variceal rebleeding, two patients died of
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Table 3 Post-TIPS rebleeding, HE, and survival TIPS ? EMB (n = 53) Rebleeding (n)
3
TIPS (n = 48) 9
p
0.042
From and cause Variceal rebleeding
1
6
0.029
Esophageal varices
1
4
0.126
Gastric varices Nonvariceal bleeding Esophageal/gastric ulcer PHG
0
2
0.082
2
3
0.566
2 0
1 2
0.613 0.082
HE (n)
10
18
0.037
Death (n)
14
16
0.447
Causes of death Variceal bleeding
0
2
0.082
Progressive liver failure
9
10
0.621
HCC
2
1
0.613
Sepsis
1
1
0.944
Peritonitis
2
1
0.613
Cerebral vascular accident
0
1
0.221
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, PHG portal hypertensive gastropathy, HE hepatic encephalopathy, HCC hepatocellular carcinoma
Fig. 3 Kaplan–Meier estimation of survival among all patients undergoing TIPS with adjunctive embolotherapy versus TIPS alone (p = 0.466). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
Survival Death occurred in 30 patients during the follow-up period, including 16 patients in the TIPS alone group and 14 patients in the TIPS ? embolization group (p = 0.447). Kaplan– Meier estimation of cumulative survival for all patients after 1, 3, and 5 years was 95, 77.1, and 53.9 %, respectively. The corresponding cumulative survival rate after 1, 3, and 5 years was 88.8, 71.8, and 49.6 %, respectively, in the TIPS alone group and 94.3, 82.1, and 57.3 %, respectively, in the TIPS ? embolization group (Fig. 3). No statistically significant difference was noted between the 2 groups in terms of survival (p = 0.466). As shown in Table 3, liver dysfunction was the main etiologies. Mortality due to rebleeding occurred in 2.9 % (3 of 101 patients) during follow-up. No death due to variceal rebleeding occurred in the embolization group. HE
Fig. 2 Kaplan–Meier estimation of the probability of rebleeding among all patients in whom TIPS with adjunctive embolotherapy was performed versus TIPS alone (p = 0.048). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization
uncontrolled rebleeding. Further variceal embolization was required for three patients after rebleeding. For the remaining patients, endoscopic variceal ligation (n = 1) was performed.
During follow-up, 26 episodes of HE occurred in 18 patients (37.5 %) in the TIPS alone group and 16 episodes occurred in 10 patients (18.9 %) in the TIPS ? embolization group (p = 0.037). The probability of the absence of encephalopathy in the TIPS versus TIPS ? embolization groups was 91.7 % versus 96.2 % at 1 month, 78.1 % versus 92.5 % at 6 months, 70.8 % versus 88.5 % at 1 year, 62.6 % versus 81.1 % at 2 years, and 53.3 % versus 76.1 % at 5 years. The actuarial curves of the probability of HE were significantly higher in the TIPS alone group than in the TIPS ? embolization group (p = 0.019, Fig. 4). Most encephalopathic episodes were mild and responded well to medical therapy.
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Dig Dis Sci (2014) 59:2325–2332 Table 4 Complications of the procedures TIPS ? EMB (n = 53)
TIPS (n = 48)
p
28
23
0.622
SBP
4
5
0.613
Hepatic myelopathy
1
1
0.944
Fever
26
19
0.339
Abdominal pain
Total complications
22
16
0.397
Bacteremia
4
3
0.797
Ulcer
0
1
0.221
TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, SBP spontaneous bacterial peritonitis
Fig. 4 Kaplan–Meier estimation of the probability of HE among all patients in whom TIPS with adjunctive embolotherapy was performed versus TIPS alone (p = 0.019). TIPS transjugular intrahepatic portosystemic shunt, TIPS ? EMB transjugular intrahepatic portosystemic shunt combined with cyanoacrylate embolization, HE hepatic encephalopathy
Reduction in shunt diameter was required in 10 of 28 patients with recurrent, spontaneous encephalopathy. HE improved in all the patients after shunt diameter reduction. Complications Complications of the two procedures examined in this study are shown in Table 4. In total, 28 patients in the TIPS ? embolization group and 23 patients in the TIPS group experienced complications (p = 0.622). Spontaneous bacterial peritonitis developed in five patients in the TIPS alone group and 4 patients in the TIPS ? embolization group (p = 0.613). In addition, hepatic myelopathy developed in 1 patient in each group (p = 0.944), and both these patients received liver transplantation. As shown in Table 4, no significant inter-group differences were observed in the number of patients with other complications.
Discussion Since its introduction in the 1980s [12], the TIPS procedure has played a major role in the management of portal hypertension. In 2004, the polytetrafluoroethylene-covered Viatorr stent graft was approved by the U.S. Food and Drug Administration. This device improves shunt patency by minimizing transmural bile permeation and thereby reducing tissue ingrowth. Although the long-term patency rate has improved with the use of coated stents, the incidence of HE associated with TIPS is still a problem [13– 15].
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Variceal embolization therapy has been studied before the advent of TIPS. Lunderquist et al. [16] described percutaneous transhepatic obliteration for gastroesophageal varices in 1974. However, it has not attained widespread clinical acceptance because of the higher rebleeding rate associated with this approach [17–20]. Percutaneous transhepatic variceal embolization (PTVE) with cyanoacrylate is a modified procedure for conventional percutaneous transhepatic obliteration. With this technique, both the varices and their feeding vessels are sufficiently and permanently obliterated by cyanoacrylate. This modified PTVE technique has been confirmed as an effective and safe method for preventing variceal rebleeding [21, 22]. However, PTVE did not alleviate portal hypertension; therefore, rebleeding still occurred in approximately 20.6–46.1 % in patients in whom cyanoacrylate had not permeated the lower esophageal varices [22]. To improve the long-term results of TIPS, combination of variceal embolotherapy during TIPS creation has been described by many reports [7, 8]. Up to now, in most control trial, the bare stent was used for TIPS, and coil was used for adjunctive embolotherapy. And the results of these studies were contradictory. However, some studies argue that TIPS creation alone is sufficient to manage variceal gastrointestinal hemorrhage in most instances [23, 24]. To our knowledge, there is no published data evaluating the variceal embolotherapy with cyanoacrylate combined with TIPS versus TIPS creation alone. The purpose of this retrospective–prospective study was to compare the rebleeding rate, survival, and hepatic encephalopathy between patients treated with the two different procedures. Variceal embolotherapy with cyanoacrylate combined with TIPS insertion may be rational approach for variceal rebleeding. The combination of these two principal techniques not only decreases the portosystemic pressure gradient but also occludes the gastroesophageal varices and their feeding veins. In the present study, all patients suffering from gastroesophageal variceal hemorrhage were
Dig Dis Sci (2014) 59:2325–2332
successfully treated with TIPS alone or with variceal cyanoacrylate embolization combined with TIPS. The overall post-operative rebleeding rate was 11.9 % (12/101), but the long-term rebleeding rate in the patients treated with TIPS combined with variceal embolization was only 5.7 % (3/ 53), compared with 18.8 % (9/48) in the patients treated using TIPS alone. Thus, the rebleeding rate in the patients receiving TIPS combined with cyanoacrylate embolization was significantly lower than that in the patients treated with TIPS alone. This result may be attributed to the extensive and permanent obliteration achieved using variceal cyanoacrylate embolotherapy. Occlusion of all lower esophageal and peri- or para-esophageal varices, the submucosal varices, and the adventitial plexus of the cardia and fundus is possible using this technique. Previous reports showed that the relapse rate in patients who underwent adequate embolization of the feeding vessel to the varices was significantly lower than the rate in those with inadequate embolization [25]. Furthermore, the decreased PPG after shunts may also prevent the recanalization of the obliterated varices. The data from our results also support the findings of Tesdal et al. [9]. Although bare stent was used in their study, they embolized both the proximal and the peripheral level of the collateral vessels using long-acting occluding agents such as the combination of liquid and mechanical materials. They think that if the collateral vessels had been only placed some coils at the proximal level, it would hardly prevent the filling of distal feeder vessels and their varices. HE is a common complication after TIPS. Although most patients respond well to conservative medical therapy (i.e., restriction of dietary protein, nonabsorbable disaccharides, and nonabsorbable antibiotics), about 3–7 % of the patients treated with TIPS tend to experience recurrent or refractory encephalopathy necessitating shunt occlusion or reduction [26]. Thus, HE in cirrhotic patients following the placement of TIPS stents is still a severe problem impeding the improvement in this procedure. In this study, HE developed in 18 patients (37.5 %) in the TIPS group, but in only 10 (18.9 %) patients in the TIPS ? embolization group. This difference was statistically significant. The lower recurrence of HE in the adjunctive group may have resulted from the complete obliteration of the portosystemic shunts (the varices and their feeding veins). Furthermore, to some degree, the incidence of HE is related to the shunt diameter. In the adjunctive group, the obliteration of the varices allows for the use of smaller stent in the TIPS procedure, which also reduces the HE incidence. In terms of procedural skills, some points should be mentioned. First, embolization of gastroesophageal varices must be performed prior to stent insertion in order to achieve adequate and extensive obliteration of the lower
2331
esophageal varices and their feeding veins and to avoid introduction of cyanoacrylate into the systemic circulation. Before variceal embolotherapy, splenoportography is performed to assess the varices and the afferent veins. Then, the left gastric vein is selected for venography to determine the size of the esophageal varices, blood flow velocity, and the amount of contrast medium needed to fill the varices as well as the injection method and required quantities of cyanoacrylate. Second, cyanoacrylate must be injected slowly and continuously so that the cyanoacrylate is completely deposited around the gastroesophageal varices. Once the cyanoacrylate has been deposited in the gastric coronary vein, injection must stop immediately to prevent flow reflux and avoid introduction of cyanoacrylate into the systemic circulation. In conclusion, our results indicated that in patients with gastroesophageal variceal bleeding, TIPS combined with embolization of varices can decrease the rebleeding and HE rates compared with TIPS alone, although no survival benefit was observed. Despite the value of this finding, several important limitations of this study must be noted. First, this study was mainly retrospective and the sample was not randomized. Second, the investigation was conducted at a single hospital with a sample limited in size. A prospective, controlled trial comparing these 2 interventions is warranted to determine the optimal management.
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