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Long-term outcome of angiographic partial splenectomy in patients with decompensated liver cirrhosis and hypersplenism
Arab Journal of Gastroenterology 11 (2010) 202–205
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Long-term outcome of angiographic partial splenectomy in patients with decompensated liver cirrhosis and hypersplenism Amr Albadry a, Hasan ElSayed Elbatea b, Asem Ahmed Elfert b,⇑ a b
Department of Raadiology, Tanta University, Faculty of Medicine, Tanta, Egypt Department of Tropical Medicine and Infectious Diseases, Tanta University, Faculty of Medicine, Tanta, Egypt
a r t i c l e
i n f o
Article history: Received 28 March 2010 Accepted 19 September 2010
Keywords: Hypersplenism Angiographic partial splenectomy Partial splenic embolization
a b s t r a c t Background and study aims: Hypersplenism is one of the serious complications of splenomegaly complicating liver cirrhosis. Although partial splenic embolization has been proposed in patients with cirrhosis and thrombocytopenia, there are limited data on long-term outcome. The aim of our study was prospective evaluation of the long-term effects of angiographic partial splenectomy (APS) using polyvinyl alcohol (PVA) or gelfoam particles in patients with decompensated liver cirrhosis and hypersplenism. Patients and methods: This study was done at Radiology and Tropical Medicine of Tanta University hospitals. Sixty patients were randomly assigned to two equal groups, PVA group, and gelfoam group. Control group included 18 patients, who refused invasive procedures and treated conservatively. Informed consent was obtained from every patient. Results: All groups were matched as regards age, sex, Child class, presence of oesophageal varices and complete blood count findings. APS was successfully performed in all 60 patients. Post-embolization syndrome was the most frequent side effect in both test groups while the need for repeated transfusions was significantly higher in the control group. No significant difference in mortality for all groups was detected. Variceal bleeding was significantly more in the control group. The procedure related complications were comparable in both test groups. All blood indices have significantly improved in comparison to the control group (p < 0.05). In both test groups white blood cells (WBCs), platelets (PLT) and haemoglobin improved significantly in comparison to the pre-procedure values (p < 0.05). Post-procedure WBCs and PLT were significantly higher in the gelfoam group than those in the PVA group (p < 0.05). Conclusion: APS is effective and has a favourable long-term outcome in the treatment of hypersplenism in Egyptian patients with decompensated post-hepatitis C cirrhosis. APS decreased the need for repeated transfusions. Both types of embolizing particles (PVA and gelfoam) were comparable as regards efficacy and post-procedure complications. APS may decrease the rate of variceal bleeding and future studies are needed to clarify its effects on portal hypertension. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Partial splenectomy (PSE) has been introduced as an alternative to splenectomy in 1973 [1], but not widely used until recent years [2,3]. Although partial splenic embolization has been proposed in patients with cirrhosis and thrombocytopenia or neutropenia, there are limited data on long-term outcome [4]. PSE has also been used for treatment of portal systemic encephalopathy. The commonly used embolic materials in PSE are gelfoam particles [5]. Polyvinyl alcohol (PVA) is an embolizing material with smaller
⇑ Corresponding author. E-mail address: [email protected] (A.A. Elfert).
cubes that can reach closer to the splenic sinusoids and be more effective in the treatment of hypersplenism [6]. The aim of our study was prospective evaluation of the longterm effects of angiographic partial splenectomy (APS) using polyvinyl alcohol (PVA) or gelfoam particles in patients with decompensated liver cirrhosis and hypersplenism. Patients and methods The study was approved by the local ethical committee of Tanta University. Sixty-one patients with decompensated liver cirrhosis due to hepatitis C virus infection, splenomegaly, and hypersplenism were included in the study and followed up between January 2007 and December 2009. Patients with Child A cirrhosis,
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.09.004
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A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205 Table 1 Baseline characteristics of patients in various groups. Group I
Sex Male Female Age (years) Child-Pugh class B C Oesophageal varices
Group II
Group III
n = 30
%
n = 30
%
n = 18
%
22 8
73 27 46.2 + 8.9
19 11
63 37 47.1 + 7.3
13 5 48.1 + 5.3
72 28
24 6 18
80* 20 60
21 9 15
70 30 50
11 7 10
61 39 56
CBC WBCs (103 L 1) PLT (103 L 1) RBC (1012 L 1) Hb% *
p 2.32 ± 0.40 41 ± 0.50 3.40 ± 0.55 8 ± 1.2
2.24 ± 0.50 37 ± 0.60 3.35 ± 0.80 7.4 ± 1.6
2.42 ± 1.40 65 ± 12.29 3.66 ± 0.95 8.3 ± 1.3
>0.05 >0.05 >0.05 >0.05
Significant difference between results in this group and the control group at p < 0.05.
encephalopathy, bilirubin >3 mg/dl, those with peritonitis or cancer and those with uncontrolled diabetes, significant renal or heart disease were excluded from the study. Patients with bone marrow suppression were excluded. Patients with hepatitis B were also excluded as they were few in our hospital. Informed consent was obtained from every patient before the procedure. One patient has been excluded because of failure to selectively cannulate the final branches of a hugely dilated and tortuous splenic artery for fear of backwash and embolization of the hepatic artery branches. The remaining 60 patients were randomized into two equal test groups. A control group consisted of 18 patients who refused invasive procedures and were treated conservatively with repeated transfusions. All groups were matched as regard age, sex, and preoperative peripheral blood count (CBC). Table 1 demonstrates the patient characteristics in both groups. Group I had significantly more Child class B patients in comparison to the control group. The diagnosis of hypersplenism was done by CBC and confirmed by bone marrow (BM) examination. Complete preoperative evaluation and preparation were done at the Department of Tropical
Medicine and Infectious Diseases, Tanta University Hospitals. Intensive medical therapy has been used to control ascites. Also, platelets, fresh frozen plasma (FFP), and packed red blood cells transfusions were done when needed. INR 61.5, platelet count P100,000/mm3, and creatinine <2 mg/dl were prerequisites of the procedure. Oesophagogastroduodenoscopy was done for all patients in all groups using Olympus GIF-Q160 videoscope and large oesophageal varices were obliterated using Saeed Multishooter band ligator (Wilson-Cook, USA) on biweekly intervals before the procedure. Preoperative antibiotic prophylaxis was given one hour before the procedure. Under aseptic conditions, and with local xylocaine infiltration, a 5 F catheter (Cook, Bloomington, USA) was inserted into the femoral artery by the Seldinger method [7]. Coeliac and selective splenic arterial angiography was performed to observe the distribution of splenic arteries and collaterals. The tip of the catheter was advanced towards the hilum of the spleen as far as possible (Fig. 1). Then, embolization was done using PVA (300–500 lm) in group I and gelfoam (1–2 mm) particles in group II, suspended in contrast medium and 20 mg gentamicin sulfate. One 2 6 cm sheet divided
Fig. 1. Pre-embolization splenic angiogram showing splenomegaly and dilated tortuous splenic artery.
Fig. 2. Post-embolisation of the splenic artery branches (more than 70%).
204
A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205
Postoperative management included antibiotics (amoxycillineclavulinate 1.2 g bid, and ciprofloxacine 500 mg bid I.V.), domperidone 60 mg bid rectal, ranitidine 150 mg bid I.V., and paracetamol 1 g bid I.V. Patients were hospitalized until the acute post-embolization syndrome attenuated, then follow up continued in the outpatient clinic. CBC, serum bilirubin, blood sugar, liver enzymes and abdominal ultrasonogram were done before the procedure and on the 3rd, 7th, 14th, and 30th day after the procedure and then every 3 months thereafter up to one year. Statistical analysis was done using the paired t-test to compare pre- and post-embolization in the same group, the unpaired t-test to compare parametric data between groups, and Chi-square to compare non parametric variables. p values less than 0.05 were considered statistically significant. Results Fig. 3. Splenic abscess complicating more than 70% embolisation.
into 1–2 mm particles in the gelfoam group or 5 ml of PVA particles were needed to occlude 50–70% of the splenic artery branches. The extent of embolization was set to be 50–70%. This was achieved through repeated injections of particles under angiographic control. After each injection, the extent of embolization was assessed by rough estimation of the percentage of ablated area of splenic parenchyma compared to pre-embolization angiography. This was judged simultaneously by both the radiologist and the assistant (Fig. 2). The precise extent of embolization was calculated on CT examination 2 weeks after the procedure, compared to pre-procedure CT scan. Abdominal CT scanning was done with Light Speed QX/ICT scanner (GE Medical Systems, Milwaukee, WI, USA).
There was no significant difference between both groups regarding age, sex or baseline CBC findings. Group I had significantly more Child class B patients compared to the control group (Table 1). APS was successfully performed in all 60 patients in the test groups. 46 patients (76.67%) completed the 3 years follow up; 25 (83%) in group I, and 22 (73%) in group II, in comparison to 12 (67%) in the control group. In both test groups WBCs, PLT, and haemoglobin improved significantly in comparison to the pre-procedure values (p < 0.05) within one month. These were also significantly increased than that the control group after the procedure. Also, WBCs and platelets were significantly increased in group II than in group I patients (p < 0.05) (Table 2). Post-embolization syndrome was the most frequent side effect consisting of abdominal pain, fever, nausea, and vomiting. It
Table 2 Postoperative CBC changes in both test groups compared to the control group. Group I
Hb% RBCs (1012 L 1) WBCs (103 L 1) PLT (103 L 1) * #
Group II
Group III
Before
After
Before
After
Before
After
8 ± 1.2 3.4 ± 0.55 2.32 ± 0.40 41 ± 0.50
11.6 ± 2.3* 3.9 ± 0.9 5.12 ± 0.33* 193 ± 0.61*
7.4 ± 1.6 3.35 ± 0.80 2.24 ± 0.50 37 ± 0.60
12.1 ± 0.9* 4.05 ± 0.21* 7.04 ± 0.75*,# 237 ± 0.85*,#
8.3 ± 1.3 3.66 ± 0.95 2.42 ± 1.4 65 ± 12.29
9.1 ± 0.9 3.75 ± 0.72 2.54 ± 0.64 68 ± 2.39
Significant difference between results before and after treatment in the same group at p < 0.05 and in comparison with the control group at p < 0.01. Significant difference between results after treatment between both test groups at p < 0.05.
Table 3 Prognosis of patients with hypersplenism after APS using PVA and gelfoam particles compared to conservative treatment. Group I n = 30 Hospital stay Post-embolization syndrome Need for a second embolization Procedure related death with HRF Recurrent blood transfusion Died of HCC Died of hepatocellular failure Bacterial peritonitis Splenic abscess Variceal bleeding Portal vein thrombosis Lost to follow up * #
2.4 ± 3.7 29 1 0 0 1 1 1 2 1 1 2
Group II
Group III
%
n = 30
%
n = 18
%
–
3.33 0 0 3.33 3.33 3.33 6.67 3.33 3.33 6.67
2.1 ± 1.7 28 2 1 0 1 4# 0 3 0 1 1
25 ± 4.5 – – – 18 1 2 2 0 3 0 2
– – – 100* 5.55 11 11 0 16.67* 0 11
Significant difference between test groups and the control group at p < 0.05. Significant difference between results after treatment between both test groups at p < 0.05.
6.67 3.33 0 3.33 13.33 0 10 0 3.33 3.33
A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205
occurred in 29 (96.67%) patients of group I and in 28 (93.33%) of those in group II. The two patients who did not suffer had 650% embolization and both needed re-embolization within 6 months. The duration of this syndrome ranged from 6 to 26 days, with no significant difference between both groups. Five patients (two in group I and three in group II) had splenic abscess within the first month of follow up; two (one in each group) were referred for surgical splenectomy, and three (two in group I and one in group II) treated with percutaneous drainage and antibiotic therapy (Fig. 3). One patient (3.33%) had bacterial peritonitis in group I in comparison to two (11%) patients in the control group. One patient (3.33%) in group I had variceal bleeding in comparison to three patients (16.67%) in the control group. The difference was statistically significant (p < 0.05). One patient in each group died from hepatocellular carcinoma (HCC) after 9–18 months. One patient in group I, four patients in group II, and two patients in the control group died of hepatocellular failure after 3–32 months. The difference was statistically significant (p < 0.05) between groups I and II. Five patients were lost to follow up. A statistically significant increase in the rate of recurrent blood transfusions and variceal bleeding was found in the control group when compared to both test groups (Table 3). Discussion Hypersplenism is a common problem in patients with decompensated cirrhosis; the most common cause of the latter in Egypt is chronic hepatitis C. Multiple transfusions do not solve the problem radically. Splenectomy is often associated with an increased long-term risk of septic events [7]. Partial splenectomy has been introduced as a good alternative to prevent postsplenectomy infections [8]. PSE has been used instead of splenectomy to avoid excessive adhesions that may interfere with liver transplant operation, which might be required later [9], and it has mostly replaced surgical splenectomy in the treatment of hypersplenism [2,10]. Several studies have reported the feasibility of this procedure claiming favourable results in cirrhotic patients [2,3,9]. The aim of our study was to prospectively evaluate the longterm safety and efficacy of APS using PVA compared to gelfoam particles in the management of hypersplenism complicating decompensated post-hepatitis C cirrhosis in Egyptian patients. While gelfoam particles are the most commonly used embolic material in PSE [3], PVA particles were seldom used with good short-term effects and some severe side effects [4]. The results of our study showed that APS using PVA particles was comparably safe and effective as gelfoam particles in treating hypersplenism with a good long-term outcome for both materials. APS had significantly improved CBC for more than one year of follow up and significantly minimized the need for transfusions. APS had few complications with no significant effect on the mortality of decompensated cirrhotic patients. In our study, the patients who needed repeating the procedure within 6 months, as the CBC improvements rapidly reversed, are those who had around 50% infarction area. This was in accordance with Zhu et al. [11] who recommended that the second phase of PSE should be given if the splenic infarction rate does not reach the intended 50% of splenic volume. Also, it was in accordance with Watanabe et al. [12] who stated that re-embolization is not likely to be necessary in the majority of patients who have had splenic embolization with an infarction rate of >80%. In our study, the peak change in the CBC findings was mostly after 3 days of procedure and then gradually decreased. This is in
205
accordance to the findings of Zhu et al. [11] who recorded the peak level on the third day and in the second week after PSE, respectively, and then gradually fell during the follow up period. They explained this fall by splenic regeneration after PSE, as they observed the long-term changes in splenic volumes after PSE. In our study, we tried to limit embolization between 50% and 70%. This has been accomplished in most of our patients. We had 93–97% post-embolization syndrome with few complications and good efficacy and infrequent need for repeating the procedure. In accordance with our results, Sangro et al. [13] reported that post-embolization syndrome was the most frequent side effect (85.5%), which was usually tolerable to the patients themselves and was easily controlled via conservative therapy. In accordance with Tagiri et al. [2], N’Kontchou et al. [4], Yoshida et al. [5], Nio et al. [9], and Zhu et al. [11], the long-term results of our study were good and satisfactory. Significant reduction of variceal bleeding has been noted after APS, but one should take into consideration that the relatively smaller number of patients and the pre-procedure prophylactic band ligation that may have altered the natural course of portal hypertension and its complications. APS has been associated with significant increase in splenic abscess formation and splenic vein thrombosis, but this should be compared to the historical complications of surgical splenectomy. Also, the increased incidence of liver cell failure should be evaluated in larger number of patients, but this is expected as these patients with decompensated liver disease are poor surgical candidates. In conclusion, APS using either PVA or gelfoam particles is safe and effective and has a good long-term outcome in the treatment of hypersplenism in Egyptian patients with decompensated liver cirrhosis due to chronic hepatitis C infection. Future studies are encouraged to test the effect of APS on portal hypertension and variceal bleeding. Conflicts of interest The authors declared that there was no conflict of interest. References [1] Maddison FE. Embolic therapy of hypersplenism. Invest Radiol 1973;8:280–1. [2] Tajiri T, Onda M, Yoshida H, et al. Long-term hematological and biochemical effects of partial splenic embolization in hepatic cirrhosis. Hepatogastroenterology 2002;49(47):1445–8. [3] Kimura F, Ito H, Shimizu H, et al. Partial splenic embolization for the treatment of hereditary spherocytosis. AJR Am J Roentgenol 2003;181(4):1021–4. [4] N’Kontchou G, Seror O, Bourcier V, et al. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol 2005;17(2):179–84. [5] Yoshida H, Mamada Y, Taniai N, et al. Long-term results of partial splenic artery embolization as supplemental treatment for portal-systemic encephalopathy. Am J Gastroenterol 2005;100(1):43–7. [6] Sternbach G. Sven Ivar Seldinger: Catheter introduction on a flexible leader. J Emerg Med 1990;8(5):635–7. [7] Winslow ER, Brunt LM. Perioperative outcomes of laparoscopic versus open splenectomy: a meta-analysis with an emphasis on complications. Surgery 2003;134(4):647–53. discussion 654–655. [8] Hall JG, Kurtzberg J, Szabolcs P, et al. Partial splenectomy before a hematopoietic stem cell transplantation in children. J Pediatr Surg 2005;40(1):221–7. [9] Nio M, Hayashi Y, Sano N, et al. Long-term efficacy of partial splenic embolization in children. J Pediatr Surg 2003;38(12):1760–2. [10] Yoshida H, Mamada Y, Taniai N, et al. Partial splenic embolization. Hepatol Res 2008;38(3):225–33. [11] Zhu K, Meng X, Qian J, et al. Partial splenic embolization for hypersplenism in cirrhosis: a long-term outcome in 62 patients. Dig Liver Dis 2009;41(6):411–6. [12] Watanabe Y, Todani T, Noda T. Changes in splenic volume after partial splenic embolization in children. J Pediatr Surg 1996;31(2):241–4. [13] Sangro B, Bilbao I, Herrero I, et al. Partial splenic embolization for the treatment of hypersplenism in cirrhosis. Hepatology 1993;18(2):309–14.
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Long-term outcome of angiographic partial splenectomy in patients with decompensated liver cirrhosis and hypersplenism Amr Albadry a, Hasan ElSayed Elbatea b, Asem Ahmed Elfert b,⇑ a b
Department of Raadiology, Tanta University, Faculty of Medicine, Tanta, Egypt Department of Tropical Medicine and Infectious Diseases, Tanta University, Faculty of Medicine, Tanta, Egypt
a r t i c l e
i n f o
Article history: Received 28 March 2010 Accepted 19 September 2010
Keywords: Hypersplenism Angiographic partial splenectomy Partial splenic embolization
a b s t r a c t Background and study aims: Hypersplenism is one of the serious complications of splenomegaly complicating liver cirrhosis. Although partial splenic embolization has been proposed in patients with cirrhosis and thrombocytopenia, there are limited data on long-term outcome. The aim of our study was prospective evaluation of the long-term effects of angiographic partial splenectomy (APS) using polyvinyl alcohol (PVA) or gelfoam particles in patients with decompensated liver cirrhosis and hypersplenism. Patients and methods: This study was done at Radiology and Tropical Medicine of Tanta University hospitals. Sixty patients were randomly assigned to two equal groups, PVA group, and gelfoam group. Control group included 18 patients, who refused invasive procedures and treated conservatively. Informed consent was obtained from every patient. Results: All groups were matched as regards age, sex, Child class, presence of oesophageal varices and complete blood count findings. APS was successfully performed in all 60 patients. Post-embolization syndrome was the most frequent side effect in both test groups while the need for repeated transfusions was significantly higher in the control group. No significant difference in mortality for all groups was detected. Variceal bleeding was significantly more in the control group. The procedure related complications were comparable in both test groups. All blood indices have significantly improved in comparison to the control group (p < 0.05). In both test groups white blood cells (WBCs), platelets (PLT) and haemoglobin improved significantly in comparison to the pre-procedure values (p < 0.05). Post-procedure WBCs and PLT were significantly higher in the gelfoam group than those in the PVA group (p < 0.05). Conclusion: APS is effective and has a favourable long-term outcome in the treatment of hypersplenism in Egyptian patients with decompensated post-hepatitis C cirrhosis. APS decreased the need for repeated transfusions. Both types of embolizing particles (PVA and gelfoam) were comparable as regards efficacy and post-procedure complications. APS may decrease the rate of variceal bleeding and future studies are needed to clarify its effects on portal hypertension. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Partial splenectomy (PSE) has been introduced as an alternative to splenectomy in 1973 [1], but not widely used until recent years [2,3]. Although partial splenic embolization has been proposed in patients with cirrhosis and thrombocytopenia or neutropenia, there are limited data on long-term outcome [4]. PSE has also been used for treatment of portal systemic encephalopathy. The commonly used embolic materials in PSE are gelfoam particles [5]. Polyvinyl alcohol (PVA) is an embolizing material with smaller
⇑ Corresponding author. E-mail address: [email protected] (A.A. Elfert).
cubes that can reach closer to the splenic sinusoids and be more effective in the treatment of hypersplenism [6]. The aim of our study was prospective evaluation of the longterm effects of angiographic partial splenectomy (APS) using polyvinyl alcohol (PVA) or gelfoam particles in patients with decompensated liver cirrhosis and hypersplenism. Patients and methods The study was approved by the local ethical committee of Tanta University. Sixty-one patients with decompensated liver cirrhosis due to hepatitis C virus infection, splenomegaly, and hypersplenism were included in the study and followed up between January 2007 and December 2009. Patients with Child A cirrhosis,
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.09.004
203
A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205 Table 1 Baseline characteristics of patients in various groups. Group I
Sex Male Female Age (years) Child-Pugh class B C Oesophageal varices
Group II
Group III
n = 30
%
n = 30
%
n = 18
%
22 8
73 27 46.2 + 8.9
19 11
63 37 47.1 + 7.3
13 5 48.1 + 5.3
72 28
24 6 18
80* 20 60
21 9 15
70 30 50
11 7 10
61 39 56
CBC WBCs (103 L 1) PLT (103 L 1) RBC (1012 L 1) Hb% *
p 2.32 ± 0.40 41 ± 0.50 3.40 ± 0.55 8 ± 1.2
2.24 ± 0.50 37 ± 0.60 3.35 ± 0.80 7.4 ± 1.6
2.42 ± 1.40 65 ± 12.29 3.66 ± 0.95 8.3 ± 1.3
>0.05 >0.05 >0.05 >0.05
Significant difference between results in this group and the control group at p < 0.05.
encephalopathy, bilirubin >3 mg/dl, those with peritonitis or cancer and those with uncontrolled diabetes, significant renal or heart disease were excluded from the study. Patients with bone marrow suppression were excluded. Patients with hepatitis B were also excluded as they were few in our hospital. Informed consent was obtained from every patient before the procedure. One patient has been excluded because of failure to selectively cannulate the final branches of a hugely dilated and tortuous splenic artery for fear of backwash and embolization of the hepatic artery branches. The remaining 60 patients were randomized into two equal test groups. A control group consisted of 18 patients who refused invasive procedures and were treated conservatively with repeated transfusions. All groups were matched as regard age, sex, and preoperative peripheral blood count (CBC). Table 1 demonstrates the patient characteristics in both groups. Group I had significantly more Child class B patients in comparison to the control group. The diagnosis of hypersplenism was done by CBC and confirmed by bone marrow (BM) examination. Complete preoperative evaluation and preparation were done at the Department of Tropical
Medicine and Infectious Diseases, Tanta University Hospitals. Intensive medical therapy has been used to control ascites. Also, platelets, fresh frozen plasma (FFP), and packed red blood cells transfusions were done when needed. INR 61.5, platelet count P100,000/mm3, and creatinine <2 mg/dl were prerequisites of the procedure. Oesophagogastroduodenoscopy was done for all patients in all groups using Olympus GIF-Q160 videoscope and large oesophageal varices were obliterated using Saeed Multishooter band ligator (Wilson-Cook, USA) on biweekly intervals before the procedure. Preoperative antibiotic prophylaxis was given one hour before the procedure. Under aseptic conditions, and with local xylocaine infiltration, a 5 F catheter (Cook, Bloomington, USA) was inserted into the femoral artery by the Seldinger method [7]. Coeliac and selective splenic arterial angiography was performed to observe the distribution of splenic arteries and collaterals. The tip of the catheter was advanced towards the hilum of the spleen as far as possible (Fig. 1). Then, embolization was done using PVA (300–500 lm) in group I and gelfoam (1–2 mm) particles in group II, suspended in contrast medium and 20 mg gentamicin sulfate. One 2 6 cm sheet divided
Fig. 1. Pre-embolization splenic angiogram showing splenomegaly and dilated tortuous splenic artery.
Fig. 2. Post-embolisation of the splenic artery branches (more than 70%).
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A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205
Postoperative management included antibiotics (amoxycillineclavulinate 1.2 g bid, and ciprofloxacine 500 mg bid I.V.), domperidone 60 mg bid rectal, ranitidine 150 mg bid I.V., and paracetamol 1 g bid I.V. Patients were hospitalized until the acute post-embolization syndrome attenuated, then follow up continued in the outpatient clinic. CBC, serum bilirubin, blood sugar, liver enzymes and abdominal ultrasonogram were done before the procedure and on the 3rd, 7th, 14th, and 30th day after the procedure and then every 3 months thereafter up to one year. Statistical analysis was done using the paired t-test to compare pre- and post-embolization in the same group, the unpaired t-test to compare parametric data between groups, and Chi-square to compare non parametric variables. p values less than 0.05 were considered statistically significant. Results Fig. 3. Splenic abscess complicating more than 70% embolisation.
into 1–2 mm particles in the gelfoam group or 5 ml of PVA particles were needed to occlude 50–70% of the splenic artery branches. The extent of embolization was set to be 50–70%. This was achieved through repeated injections of particles under angiographic control. After each injection, the extent of embolization was assessed by rough estimation of the percentage of ablated area of splenic parenchyma compared to pre-embolization angiography. This was judged simultaneously by both the radiologist and the assistant (Fig. 2). The precise extent of embolization was calculated on CT examination 2 weeks after the procedure, compared to pre-procedure CT scan. Abdominal CT scanning was done with Light Speed QX/ICT scanner (GE Medical Systems, Milwaukee, WI, USA).
There was no significant difference between both groups regarding age, sex or baseline CBC findings. Group I had significantly more Child class B patients compared to the control group (Table 1). APS was successfully performed in all 60 patients in the test groups. 46 patients (76.67%) completed the 3 years follow up; 25 (83%) in group I, and 22 (73%) in group II, in comparison to 12 (67%) in the control group. In both test groups WBCs, PLT, and haemoglobin improved significantly in comparison to the pre-procedure values (p < 0.05) within one month. These were also significantly increased than that the control group after the procedure. Also, WBCs and platelets were significantly increased in group II than in group I patients (p < 0.05) (Table 2). Post-embolization syndrome was the most frequent side effect consisting of abdominal pain, fever, nausea, and vomiting. It
Table 2 Postoperative CBC changes in both test groups compared to the control group. Group I
Hb% RBCs (1012 L 1) WBCs (103 L 1) PLT (103 L 1) * #
Group II
Group III
Before
After
Before
After
Before
After
8 ± 1.2 3.4 ± 0.55 2.32 ± 0.40 41 ± 0.50
11.6 ± 2.3* 3.9 ± 0.9 5.12 ± 0.33* 193 ± 0.61*
7.4 ± 1.6 3.35 ± 0.80 2.24 ± 0.50 37 ± 0.60
12.1 ± 0.9* 4.05 ± 0.21* 7.04 ± 0.75*,# 237 ± 0.85*,#
8.3 ± 1.3 3.66 ± 0.95 2.42 ± 1.4 65 ± 12.29
9.1 ± 0.9 3.75 ± 0.72 2.54 ± 0.64 68 ± 2.39
Significant difference between results before and after treatment in the same group at p < 0.05 and in comparison with the control group at p < 0.01. Significant difference between results after treatment between both test groups at p < 0.05.
Table 3 Prognosis of patients with hypersplenism after APS using PVA and gelfoam particles compared to conservative treatment. Group I n = 30 Hospital stay Post-embolization syndrome Need for a second embolization Procedure related death with HRF Recurrent blood transfusion Died of HCC Died of hepatocellular failure Bacterial peritonitis Splenic abscess Variceal bleeding Portal vein thrombosis Lost to follow up * #
2.4 ± 3.7 29 1 0 0 1 1 1 2 1 1 2
Group II
Group III
%
n = 30
%
n = 18
%
–
3.33 0 0 3.33 3.33 3.33 6.67 3.33 3.33 6.67
2.1 ± 1.7 28 2 1 0 1 4# 0 3 0 1 1
25 ± 4.5 – – – 18 1 2 2 0 3 0 2
– – – 100* 5.55 11 11 0 16.67* 0 11
Significant difference between test groups and the control group at p < 0.05. Significant difference between results after treatment between both test groups at p < 0.05.
6.67 3.33 0 3.33 13.33 0 10 0 3.33 3.33
A. Albadry et al. / Arab Journal of Gastroenterology 11 (2010) 202–205
occurred in 29 (96.67%) patients of group I and in 28 (93.33%) of those in group II. The two patients who did not suffer had 650% embolization and both needed re-embolization within 6 months. The duration of this syndrome ranged from 6 to 26 days, with no significant difference between both groups. Five patients (two in group I and three in group II) had splenic abscess within the first month of follow up; two (one in each group) were referred for surgical splenectomy, and three (two in group I and one in group II) treated with percutaneous drainage and antibiotic therapy (Fig. 3). One patient (3.33%) had bacterial peritonitis in group I in comparison to two (11%) patients in the control group. One patient (3.33%) in group I had variceal bleeding in comparison to three patients (16.67%) in the control group. The difference was statistically significant (p < 0.05). One patient in each group died from hepatocellular carcinoma (HCC) after 9–18 months. One patient in group I, four patients in group II, and two patients in the control group died of hepatocellular failure after 3–32 months. The difference was statistically significant (p < 0.05) between groups I and II. Five patients were lost to follow up. A statistically significant increase in the rate of recurrent blood transfusions and variceal bleeding was found in the control group when compared to both test groups (Table 3). Discussion Hypersplenism is a common problem in patients with decompensated cirrhosis; the most common cause of the latter in Egypt is chronic hepatitis C. Multiple transfusions do not solve the problem radically. Splenectomy is often associated with an increased long-term risk of septic events [7]. Partial splenectomy has been introduced as a good alternative to prevent postsplenectomy infections [8]. PSE has been used instead of splenectomy to avoid excessive adhesions that may interfere with liver transplant operation, which might be required later [9], and it has mostly replaced surgical splenectomy in the treatment of hypersplenism [2,10]. Several studies have reported the feasibility of this procedure claiming favourable results in cirrhotic patients [2,3,9]. The aim of our study was to prospectively evaluate the longterm safety and efficacy of APS using PVA compared to gelfoam particles in the management of hypersplenism complicating decompensated post-hepatitis C cirrhosis in Egyptian patients. While gelfoam particles are the most commonly used embolic material in PSE [3], PVA particles were seldom used with good short-term effects and some severe side effects [4]. The results of our study showed that APS using PVA particles was comparably safe and effective as gelfoam particles in treating hypersplenism with a good long-term outcome for both materials. APS had significantly improved CBC for more than one year of follow up and significantly minimized the need for transfusions. APS had few complications with no significant effect on the mortality of decompensated cirrhotic patients. In our study, the patients who needed repeating the procedure within 6 months, as the CBC improvements rapidly reversed, are those who had around 50% infarction area. This was in accordance with Zhu et al. [11] who recommended that the second phase of PSE should be given if the splenic infarction rate does not reach the intended 50% of splenic volume. Also, it was in accordance with Watanabe et al. [12] who stated that re-embolization is not likely to be necessary in the majority of patients who have had splenic embolization with an infarction rate of >80%. In our study, the peak change in the CBC findings was mostly after 3 days of procedure and then gradually decreased. This is in
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accordance to the findings of Zhu et al. [11] who recorded the peak level on the third day and in the second week after PSE, respectively, and then gradually fell during the follow up period. They explained this fall by splenic regeneration after PSE, as they observed the long-term changes in splenic volumes after PSE. In our study, we tried to limit embolization between 50% and 70%. This has been accomplished in most of our patients. We had 93–97% post-embolization syndrome with few complications and good efficacy and infrequent need for repeating the procedure. In accordance with our results, Sangro et al. [13] reported that post-embolization syndrome was the most frequent side effect (85.5%), which was usually tolerable to the patients themselves and was easily controlled via conservative therapy. In accordance with Tagiri et al. [2], N’Kontchou et al. [4], Yoshida et al. [5], Nio et al. [9], and Zhu et al. [11], the long-term results of our study were good and satisfactory. Significant reduction of variceal bleeding has been noted after APS, but one should take into consideration that the relatively smaller number of patients and the pre-procedure prophylactic band ligation that may have altered the natural course of portal hypertension and its complications. APS has been associated with significant increase in splenic abscess formation and splenic vein thrombosis, but this should be compared to the historical complications of surgical splenectomy. Also, the increased incidence of liver cell failure should be evaluated in larger number of patients, but this is expected as these patients with decompensated liver disease are poor surgical candidates. In conclusion, APS using either PVA or gelfoam particles is safe and effective and has a good long-term outcome in the treatment of hypersplenism in Egyptian patients with decompensated liver cirrhosis due to chronic hepatitis C infection. Future studies are encouraged to test the effect of APS on portal hypertension and variceal bleeding. Conflicts of interest The authors declared that there was no conflict of interest. References [1] Maddison FE. Embolic therapy of hypersplenism. Invest Radiol 1973;8:280–1. [2] Tajiri T, Onda M, Yoshida H, et al. Long-term hematological and biochemical effects of partial splenic embolization in hepatic cirrhosis. Hepatogastroenterology 2002;49(47):1445–8. [3] Kimura F, Ito H, Shimizu H, et al. Partial splenic embolization for the treatment of hereditary spherocytosis. AJR Am J Roentgenol 2003;181(4):1021–4. [4] N’Kontchou G, Seror O, Bourcier V, et al. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol 2005;17(2):179–84. [5] Yoshida H, Mamada Y, Taniai N, et al. Long-term results of partial splenic artery embolization as supplemental treatment for portal-systemic encephalopathy. Am J Gastroenterol 2005;100(1):43–7. [6] Sternbach G. Sven Ivar Seldinger: Catheter introduction on a flexible leader. J Emerg Med 1990;8(5):635–7. [7] Winslow ER, Brunt LM. Perioperative outcomes of laparoscopic versus open splenectomy: a meta-analysis with an emphasis on complications. Surgery 2003;134(4):647–53. discussion 654–655. [8] Hall JG, Kurtzberg J, Szabolcs P, et al. Partial splenectomy before a hematopoietic stem cell transplantation in children. J Pediatr Surg 2005;40(1):221–7. [9] Nio M, Hayashi Y, Sano N, et al. Long-term efficacy of partial splenic embolization in children. J Pediatr Surg 2003;38(12):1760–2. [10] Yoshida H, Mamada Y, Taniai N, et al. Partial splenic embolization. Hepatol Res 2008;38(3):225–33. [11] Zhu K, Meng X, Qian J, et al. Partial splenic embolization for hypersplenism in cirrhosis: a long-term outcome in 62 patients. Dig Liver Dis 2009;41(6):411–6. [12] Watanabe Y, Todani T, Noda T. Changes in splenic volume after partial splenic embolization in children. J Pediatr Surg 1996;31(2):241–4. [13] Sangro B, Bilbao I, Herrero I, et al. Partial splenic embolization for the treatment of hypersplenism in cirrhosis. Hepatology 1993;18(2):309–14.