Cardiovasc Intervent Radiol DOI 10.1007/s00270-013-0595-1
CLINICAL INVESTIGATION
Interventional Radiological Treatment of Perihepatic Vascular Stenosis or Occlusion in Pediatric Patients After Liver Transplantation Wibke Uller • Birgit Knoppke • Andreas G. Schreyer • Peter Heiss • Hans J. Schlitt • Michael Melter • Christian Stroszczynski • Niels Zorger Walter A. Wohlgemuth
•
Received: 4 November 2012 / Accepted: 10 February 2013 Ó Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013
Abstract Purpose Evaluation of the efficacy and safety of percutaneous treatment of vascular stenoses and occlusions in pediatric liver transplant recipients. Methods Fifteen children (mean age 8.3 years) underwent interventional procedures for 18 vascular complications after liver transplantation. Patients had stenoses or occlusions of portal veins (n = 8), hepatic veins (n = 3), inferior vena cava (IVC; n = 2) or hepatic arteries (n = 5). Technical and clinical success rates were evaluated. Results Stent angioplasty was performed in seven cases (portal vein, hepatic artery and IVC), and sole balloon angioplasty was performed in eight cases. One child underwent thrombolysis (hepatic artery). Clinical and technical success was achieved in 14 of 18 cases of vascular stenoses or occlusions (mean follow-up 710 days). Conclusion Pediatric interventional radiology allows effective and safe treatment of vascular stenoses after W. Uller (&) A. G. Schreyer P. Heiss C. Stroszczynski N. Zorger W. A. Wohlgemuth Department of Radiology, University Medical Center Regensburg, 93053 Regensburg, Germany e-mail:
[email protected];
[email protected] B. Knoppke M. Melter KUNO University Children’s Hospital Regensburg, University Medical Center Regensburg, 93053 Regensburg, Germany H. J. Schlitt Department of Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany Present Address: N. Zorger Department of Radiology, Krankenhaus Barmherzige Bru¨der, Pru¨feninger Straße 86, 93049 Regensburg, Germany
pediatric liver transplantation (PLT). Individualized treatment with special concepts for each pediatric patient is necessary. The variety, the characteristics, and the individuality of interventional management of all kinds of possible vascular stenoses or occlusions after PLT are shown. Keywords Pediatric interventions Pediatric liver transplantation Arterial intervention Venous intervention Portal vein intervention
Introduction Liver transplantation is the standard of care for pediatric patients with end-stage liver disease or irresectable primary hepatic tumors [1, 2]. Due to the rare availability of pediatric donor livers of appropriate size, most pediatric liver transplantations (PLTs) are performed by using partial liver transplants mostly consisting of the two left-lateral segments (II and III) either from dead or living donors. Advances in surgical and immunosuppressive therapy and perioperative management further contributed to a significantly prolonged survival [3]. Nevertheless, vascular complications remain a relevant problem. Donor and recipient differences in vessel diameters, neointima hyperplasia, graft or child growth, and graft torsion increase the risk of vascular complications and may negatively influence the outcome [4–7]. Vascular complications that occur after PLT are associated with high morbidity, graft loss and mortality [8]. Portal vein stenosis has been reported to occur in 4–8 %, inferior vena cava (IVC) stenosis in \1 %, hepatic vein stenosis in approximately 2 % and hepatic artery stenosis in 11–20 % of pediatric patients after liver transplantation [5, 9–11].
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In general, endovascular techniques, including intraarterial thrombolysis and percutaneous transluminal angioplasty (PTA), with or without stent implantation, are safe and effective methods for the treatment of these vascular complications [12–14]. However, these techniques are not widely used in the treatment of pediatric patients, but they have the potential of being a less invasive alternative to repeated surgical intervention after PLT. The aim of this study was to describe various individual customized interventional radiological procedures for the treatment of vascular complications after PLT. The technical considerations involved in each procedure are described in detail, and mid-term technical and clinical success was evaluated in these patients.
Patients and Methods Patients Between January 2007 and June 2012, 17 consecutive children underwent endovascular treatment for 20 vascular complications after liver transplantation. These included 15 children who had 18 vascular stenoses and occlusions in this series (two children will be described elsewhere). Ten children were female and five children were male; ages ranged from 8 months to 17.7 years (mean 8.3 years). Indications for liver transplantation were biliary atresia (n = 7), tyrosinemia type I (n = 1), cholangiodysplasia (n = 1), graft-versus-host disease (GVHD; n = 1), cystic fibrosis (n = 1), haemochromatosis (n = 1), mitochondriopathy (n = 2), and autoimmune hepatitis (n = 1). All patients with biliary atresia had undergone at least one Kasai surgery before transplantation. Two children underwent a whole liver transplant, six children a reduced-size transplant (three to six segments), and seven children received a left-lateral lobe (segments II and III). Four children were transplanted for the second time and one child for the third time. The time interval between liver transplantation and the first interventional procedure ranged from 6 to 3,041 days (mean 952) (Table 1). Six children underwent reoperations between liver transplantation and radiological intervention (Table 2). The diagnosis of vascular stenoses was based on results of Doppler ultrasound, computed tomography or magnetic resonance imaging in combination with clinical and laboratory data. Standard postprocedural controls consisted of clinical, laboratory and color Doppler ultrasound examinations. Color Doppler ultrasound was routinely performed on day 1 after the intervention as baseline evaluation, which was compared with the findings at follow-up ultrasound evaluations. Imaging and clinical follow-up was performed at least every 3 months during the first postprocedural year and
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then every 6–12 months. Clinical success was defined by resolution or marked improvement of clinical signs, symptoms, and laboratory and imaging data compared with observations before the intervention. Methods The procedures were performed with the patient under general anesthesia or monitored anesthesia with spontaneous respiration and additional local anesthesia. Every patient received 100 IU of heparin/kg body weight at the beginning of the intervention (maximum permissible dose 5,000 IU). Balloon angioplasty was performed with sizes adapted to the diameter of the vessels at a pressure of 8–11 atm and prolonged balloon inflation (3 min). The procedural success of the vascular treatments was defined as absence or decrease of stenosis (\30 % residual stenosis) at arteriography or venography. Pressure gradients were measured when angiographic findings alone were not meaningful. Portal Vein In patients with portal vein stenosis, transhepatic puncture of the portal vein was performed using a 21-gauge needle (CHIBA; Boston Scientific, Natick, MA) under ultrasound guidance. The Accustick Introducer System (Boston Scientific) was advanced over a Cope wire (Cook, Bjaeverskov, Denmark) to a central portal branch. The Accustick sheath was exchanged for vascular sheaths up to size 6F. Balloon angioplasty (balloons of 2.5–12 mm) and, in three cases of recoiling after balloon angioplasty, stent angioplasty followed [Epic (7 9 19 mm); Boston Scientific (patients no. 5 and 8); and Astron Pulsar Biotronic (6 mm 9 3 cm); Bu¨lach, Switzerland (patient no. 6)]. In four cases of occlusion or stenosis of the portal vein, we preferred a transsplenic approach to reach the extrahepatic portal circulation (patients no. 3, 6, and 7). Puncture of an intrasplenic central branch of the splenic vein was performed using ultrasound guidance and a CHIBA needle. After introducing the Cope wire under fluoroscopic guidance, the Accustick Introducer System was advanced into the splenic vein. For recanalization of the portal vein, a combination of microcatheters (Progreat, Terumo, Leuven, Belgium), 4F catheters (RIM, Cook), and 0.035-inch hydrophilic guidewires (Terumo) was used. IVC and Hepatic Vein In cases of completely obstructed IVC and stenosis, we used a femoral access to cross and recanalize the IVC with a 4F catheter and a 0.035-inch hydrophilic guidewire. Balloon angioplasty (6.0–9.0 mm) and IVC stenting
W. Uller et al.: Interventions After PLT Table 1 Patients and PLTs Patient no.
Sex
Age at first intervention
Indication for PLT
Type of graft (liver segments) and donor
Interval between PLT and (1st) intervention
Stenosis
1
M
17 years 8 months
Tyrosinemia type I
Whole liver; deceased
3,041 days
Portal vein stenosis
2
F
17 years 4 months
Cholangiodysplasia
Whole liver; deceased
2,008 days
Portal vein stenosis
3
M
1 year 9 months
Neonatal hemochromatosis
II–III; deceased
623 days
Portal vein stenosis
4
F
2 years
Mitochondriopathy
II–III; deceased
49 days
Portal vein stenosis
5
F
1 years 11 months
Biliary atresia
II–III; deceased
566 days
Portal vein stenosis
6
F
8 months
Biliary atresia
II–III; deceased
77 days 86 days
Portal vein occlusion Hepatic artery stenosis
7
M
1 year 2 months
Mitochondriopathy
II–IV; deceased
322 days
Portal vein stenosis
8
F
2 years 5 months
Biliary atresia
II–III; living
509 days
Portal vein stenosis
9
F
16 years 11 months
Autoimmune hepatitis
V–VIII; living
11 days
Hepatic vein stenosis
10
F
7 years 2 months
Biliary atresia
II–III; deceased
2,330 days
Hepatic vein stenosis
2,330 days
IVC occlusion
2,430 days
IVC stenosis
11
F
12 years 10 months
Biliary atresia
II–III; deceased
2,215 days
Hepatic vein stenosis
12
M
14 years 4 months
GvHD
II, IV–VIII; deceased
506 days
Hepatic artery stenosis
13
F
4 years 7 months
Biliary atresia
II–III ?IVb; deceased
6 days
Hepatic artery dissection and occlusion
14
M
9 years 11 months
Cystic fibrosis
IV–VIII; deceased
23 days
Hepatic artery occlusion
15
F
13 years 1 months
Biliary atresia
V–VIII; living
20 days
Hepatic artery thrombosis and stenosis
followed (sinus-Repo [18 9 60 mm]; Optimed, Ettlingen, Germany [patient no. 10]). Transjugular balloon dilation (5.0–10.0 mm) of the hepatic vein and stent angioplasty (Epic [10 9 40 mm]; Boston Scientific [patient no. 7]) was performed by using a 5F multipurpose catheter (Cook) for selective catheterization.
Hepatic Artery COBRA catheters (4F and 5F; Cook) and modified RIM catheters (4F; Cook) were used to catheterize the celiac trunk by a femoral access. The RIM catheter was shortened by cutting the original 180° angle to an angle fitting to the origin of the celiac trunk. Subsequently a microcatheter [RenegadeHi-Flo with Transend-Ex-Floppy guidewire (Boston Scientific) or Progreat (Terumo)] was used. For recanalization of occlusion or dissection, various microcatheters and microguidewires with shaped tips were used.
Balloon dilation (2.5 and 5.0 mm) and stent angioplasty [Formula (5.0 9 20 mm); Cook (patient no. 12) and Enterprise (4.5 9 22 mm); Codman, Johnson & Johnson, Wokingham, UK (patient no. 6)] were performed. In case of hepatic artery thrombosis, an initial intraarterial bolus of urokinase (100,000 IE) was applied through the microcatheter, which was placed inside the thrombus. A continuous heparin drip infusion was begun with thrombolytic therapy to maintain the partial thromboplastin time between 1.5 and 2.5 times the control value. After 24 h, the procedure was repeated followed by continuous intra-arterial thrombolysis using 30,000 IE/h urokinase during 18 h. A selective control angiography followed.
Results Fifteen children after pediatric liver transplantation underwent interventional radiological procedures for a total of 18 vascular complications during a period of 66 months.
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W. Uller et al.: Interventions After PLT Table 2 Surgical revisions before radiological interventions in the same PLT Patient no.
Type of stenosis, occlusion
Surgical revisions after PLT before intervention
No. of PLTs
1
Portal vein stenosis
Second
2
Portal vein stenosis
First
3
Portal vein stenosis
First
Other complications
Portal vein stenosis Portal vein thrombosis 4
Portal vein stenosis
5 6
Portal vein stenosis Portal vein occlusion Hepatic artery stenosis
First Thrombectomy V. portae during liver transplantation
First Second
Biliary stricture (PTBD)
First
Biliary insufficiency (PTBD)
Intraperitoneal lavage (high intra-abdominal pressure, ileus) Revision jejunum (perforation) 7
Portal vein stenosis
8
Portal vein stenosis
9
Hepatic vein stenosis
10
Hepatic vein stenosis
First Packing and lavage (liver rupture and hematomas)
First Second
IVC obstruction IVC Stenosis 11
Hepatic vein stenosis
12
Hepatic artery stenosis
Revision hepaticojejunostomy (insufficiency)
First First
13
Hepatic artery dissection
Revision jejunum (perforation)
Third
14
Hepatic artery occlusion
Revision A. hepatica (shortening)
Second
Revision A. hepatica (thrombectomy)
Biliary stricture (PTBD) Extended necrosis of the liver before intervention
Revision V. portae (thrombectomy) Revision Choledochocholedochostomy (insufficiency) Packing (hematomas and diffuse bleeding) 15
Hepatic artery thrombosis and stenosis
Revision hepaticojejunostomy (insufficiency)
First
PTBD percutaneous transhepatic biliary drainage
Portal Vein Transsplenic access of the portal vein was performed four times (patients no. 3, 6, and 7) to achieve orthograde portography for optimal lesion characterization in young children with small portal branches and best conditions for recanalization in patients with portal vein occlusions and angled stenotic portal vein segments (Fig. 1). Four children with portal vein stenoses were treated successfully with balloon dilations only (patients no. 1, 2, 4, and 7). Patient no. 6 had a temporal benefit from balloon dilation, but 279 days after balloon dilation, stent angioplasty was necessary due to repeated stenosis. In two patients (patients no. 5 and 8), stenoses recoiled after balloon angioplasty, but stent angioplasty resolved the stenosis in the same session without residual stenosis (Fig. 2).
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The portal vein stenosis in patient no. 3 was resolved after the first balloon dilation, but a small thrombus remained. A second balloon angioplasty followed after 248 days, but the stenosis could not be treated successfully and the thrombus enlarged. Low molecular-weight heparin (enoxaparin 12 mg/d subcutaneous) had been applied since the first intervention, but the patient developed a subacute thrombotic occlusion of the portal vein, which could be passed neither by transhepatic nor by transsplenic access. Thus, this case could not be treated successfully. In summary, primary patency of the portal vein was achieved in six of eight children (75 %). Because one child underwent repeated angioplasty, secondary patency was achieved in seven of the eight children (87.5 %) having portal vein stenoses with durable clinical and technical success (mean follow-up 463 days).
W. Uller et al.: Interventions After PLT
Fig. 1 Portal vein stenosis in a 1-year-old boy after PLT (segments II–IV) for mitochondriopathy. A For direct orthograde portography in this young boy with short and small portal vein branches, a 4F sheath is placed in the extrahepatic portal vein (arrowhead) by way of transsplenic access. A stenosis of the portal vein is depicted (arrow).
B Portography after balloon angioplasty shows resolution of the stenosis (arrow). The 6F sheath is placed in the splenic vein (arrowhead) near the venous confluence with the superior mesenteric vein (asterisk)
IVC and Hepatic Vein Hepatic vein and IVC stenoses were treated with technical and clinical success in all three patients (patients no. 9 through 11). These patients had ascites, which dissolved after balloon dilation of the hepatic vein. In case of simultaneous stenosis of the hepatic vein and complete obstruction of the IVC without any contrast medium passage in the IVC, radiological intervention with recanalization of the
IVC led to significant clinical improvement. Renal failure, edema of the lower extremities, splenomegaly and collateral vessels resolved after angioplasty (patient no. 10). In this case, stent placement was performed due to the lack of response to balloon angioplasty alone (Fig. 3). Hepatic vein stenosis was resolved by balloon angioplasty in the same session. 4 months after IVC stent placement, a new stenosis cranial to the stent occurred, and collateral vessels and marginal ascites were detected. This stenosis was
Fig. 2 Portal vein stenosis in a 2-years-old girl after split-liver transplantation (segments II and III) for biliary atresia. A Initial portography (transhepatic access) shows stenosis of the portal vein
(arrow). B Portography after stent placement, which was performed because of recoiling of the stenosis after balloon angioplasty, shows resolution of the stenosis
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Fig. 3 Vascular complications in a 7-year-old patient after split-liver transplantation (segments II and III) for biliary atresia (simultaneous stenosis of the hepatic vein not shown). A Initial IVC venography (femoral access) shows a completely obstructed IVC and filling of collateral vessels (arrows). B IVC venography after stent deployment: The obstruction was resolved
successfully dilated by balloon angioplasty, and the collateral vessels and ascites decreased significantly. Primary patency of the stenoses was achieved in all five cases (100 %), and patients remained clinically asymptomatic during follow-up (mean 1,082 days). Hepatic Artery Primary stent placement was performed in one case with good technical and clinical result when balloon angioplasty of the hepatic artery did not show a significant success (patient no. 12; follow-up 1,222 days). Patient no. 6 underwent primary balloon angioplasty, which led to an asymptomatic period; however, 279 days after balloon angioplasty, stent angioplasty was necessary because of recurrent stenosis. Patient no. 13 had previously undergone the third liver transplant because of occlusion of the hepatic artery. Thus, it was necessary to anastomose the hepatic artery with a patch directly to the aorta. This patient developed an occlusion due to dissection during the early postoperative period. In this case, it was not possible to pass the dissection with different guidewires and catheters, so that another transplantation was required.
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In patient no. 15, the transplanted hepatic artery showed complete thrombosis 20 days after PLT. The thrombus could only be partially lysed by direct intrathrombotic administration of urokinase. After partial recanalization, two stenotic segments, one proximal and one at the anastomosis, persisted. The segmental arteries also showed partial thrombosis and multiple spasms. Continuous intraarterial thrombolysis followed, but the entire thrombotic material could not be lysed. In this case, interventional radiology had neither technical nor clinical success. This patient underwent liver retransplantation. Patient no. 14 showed complete occlusion of the hepatic artery after surgical revisions of this vessel and after abdominal packing due to hematoma and diffuse bleeding. A large liver necrosis developed before the intervention. It was not possible to recanalize this vessel. The hepatic artery was perforated with the guidewire, but no significant bleeding followed. This boy died 4 days after intervention due to hepatic failure. Primary patency rates were 20 % (one child of five), and secondary patency rates reached 40 % (two children of five) due to successfully repeated angioplasty in one child. In summary, 14 of 18 vascular stenoses or occlusions were successfully treated. Those patients were symptom-free with respect to vascular stenoses during a mean follow-up of 710 days (range 4–1,594). Interventional radiological treatment failed in four cases. In patient no 3 first balloon PTA of the portal vein was successful, but recurrent stenosis due to liver torsion and recurrent thrombus could not be resolved conservatively and by repeated PTA; thrombosis of the portal vein resulted. In patient no. 13, thrombolysis of the hepatic artery failed, and retransplantation was performed. The recanalization of hepatic artery occlusion and dissection was not successful in two children (patients no. 14 and 15). One of them died from liver failure, and the other underwent retransplantation. Thus, in 18 cases of vascular stenoses or occlusions, technical and clinical success was achieved in 14 cases. Four patients had interventional complications that did not require further therapy: one inguinal hematoma after transfemoral arterial access (patient no. 12); one guidewire perforation of the (occluded) hepatic artery (patient no. 14), which did not lead to a significant bleeding; and development of small secondary bleeding out of the percutaneous transhepatic needle tract, which required one transfusion in a previously anemic patient (patient no. 8). Partial thrombosis of the external iliac artery (femoral access in patient no. 6) was treated with heparin; the patient remained clinically asymptomatic; and the thrombosis resolved completely. Table 3 lists the performed accesses and used devices as well as the complications, technical and clinical success, and outcomes after vascular interventions.
W. Uller et al.: Interventions After PLT Table 3 Access, devices, complications, technical and clinical success, and outcomes of radiological interventions Patient no.
Complication
Access
Device
1
Portal vein stenosis
Transhepatic
2
Portal vein stenosis
Transhepatic
3
Portal vein stenosis
Complication related to intervention
Technical/ clinical success (primary assisted)
Follow-up
Outcome
Balloon
Yes/yes
Patent (1,013 days)
Alive
Balloon
Yes/yes
Patent (1,425 days)
Alive
Transhepatic
Balloon
No/no
Alive
Restenosis
Transhepatic
Balloon
Repeat angioplasty once
Thrombosis
Transhepatic/ transsplenic
4 5
Portal vein stenosis Portal vein stenosis
Transhepatic Transhepatic
6
Portal vein occlusion
Transsplenic
Balloon
Restenosis
Transsplenic/ transhepatic
Stent
Hepatic artery stenosis
Transfemoral
Balloon
Temporary partial thrombosis
Restenosis
Transfemoral
Stent
Arteria iliaca externa
7
Portal vein stenosis
Transsplenic
Balloon
8
Portal vein stenosis
Transhepatic
Stent
9
Hepatic vein stenosis
Transjugular
10
Hepatic vein stenosis
Transjugular
Complete obstruction IVC
Transfemoral
Stenosis IVC
Transjugular
Hepatic vein stenosis Hepatic artery stenosis
Transjugular Transfemoral
13
Hepatic artery dissection/occlusion
Transfemoral
14
Hepatic artery occlusion
Transfemoral
15
Hepatic artery thrombosis
Transfemoral
Subacute portal vein thrombosis Balloon Balloon
Yes/yes Yes/yes
Patent (586 days) Patent (136 days)
Alive Alive
Yes/yes
Repeat angioplasty once
Alive
Yes/yes
Repeat angioplasty once
Stent
11 12
Patent (44 days)
Patent (44 days) Yes/yes
Patent (37 days)
Alive
Yes/yes
Patent (4 days)
Alive
Stent
Yes/yes
Patent (86 days)
Alive
Balloon
Yes/yes
Patent (1,594 days)
Alive
Balloon
Yes/yes
Patent (1,594 days)
Balloon
Yes/yes
Patent (1,498 days)
Balloon Balloon
Yes/yes Yes/yes
Patent (639 days) Patent (1,222 days)
Alive Alive
No/no
Occluded
Alive (reLT)
No/no
Occluded
Died from acute liver failure
No/no
Occluded
Alive (reLT)
Needle tract bleeding
Stent
Inguinal hematoma
Stent
Small perforation hepatic artery
reLT repeat transplant
Discussion Portal Vein The percutaneous transhepatic approach is the traditional method of portal vein stenosis dilation. This approach may not be suitable in patients with coincidental portal vein thrombosis or occlusions. Therefore, we performed transsplenic accesses in cases of occlusions of the portal vein, a technique that has already been described in one child with complete portal vein thrombosis after PLT [15]. Especially in young children with occluded, small, and short portal vein branches, this approach may help to achieve optimal
conditions for recanalization and portography. The position and anatomy of the portal venous system in its intrahepatic and extrahepatic part varies after PLT, especially after split-liver PLT. Thus, recanalization by way of a transhepatic retrograde access can be unsuitable, and the antegrade transsplenic access adds valuable diagnostic information as well as an additional way to cross an unfavorable stenosis. Dilation of the venous splenic branches due to portal hypertension in these patients further increased the suitability of this approach. Using ultrasound for guidance during puncture can further avoid complications and is mandatory. In one case of necessary stent angioplasty, we combined transhepatic and transsplenic approaches due to
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a steep angle of occlusion of the extrahepatic part of the portal vein, which precluded retrograde transhepatic recanalization. Therefore, the portal vein was recanalized by a transsplenic approach; the guidewire was lanced with a snare through a previously performed transhepatic approach; and the stent could be implanted with the help of this lanced guidewire. Except in one case, we achieved patency of portal vein stenoses and occlusions in all cases with a mean follow-up of 463 days. In two children, primary stent angioplasty was performed because balloon angioplasty in the same session lead to recoiling of the stenosis, and pressure gradients decreased only between 7 and 12 mmHg. In another child, an occlusion occurred approximately 1 year after initially successful angioplasty, which necessitated stent angioplasty. In these patients, oversized (40 % oversized diameter) self-expanding stents were implanted to permit redilation of the stent in case of repeated relative stenosis after patient growth. The lengths of the stents were chosen as short as possible to permit a suitable length of unstented vessel for portal vein anastomosis in case of necessary repeated liver transplantation. The portal venous pressure gradient should be measured especially when angiographic finding are not unequivocal. It should be taken into account here that portal pressures may be misinterpreted because of venous collateral shunts [16]. Funaki et al. achieved a patency rate concerning portal vein stenosis of 100 % at 46 months after angioplasty, metallic stent placement or both together. The persistence of a pressure gradient [5 mmHg proximal and distal of the stenosis has been considered to be an indication for metallic stent placement [17]. Our findings support this consideration. IVC and Hepatic vein Hepatic venous complications in split grafts are more frequent (4 %) than in whole-liver grafts (1 %) [10]. Because reduced-size liver grafts show considerable growth, especially in pediatric recipients, this morphologic change may lead to anatomic distorsions with twisting of the veins as well as compression of the IVC. In our series, long-term patency (mean follow-up 2 years and 11 months) was achieved in all patients after angioplasty of the hepatic vein and the IVC. Complete IVC obstruction due to growth of the liver was treated successfully with stent placement when balloon dilation showed a relevant residual stenosis. Early postoperative distortion necessitated stent angioplasty of the hepatic vein in another child. Considering the future growth of the children, the largest possible stent diameters (40 % oversized diameter) and self-expanding stents were chosen. Lorenz et al. [14] reported patency rates ranging from 70 % at 3 months to 50 % at 36 months for percutaneous
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interventional procedures of venous outflow obstruction in PLT recipients. Reported cases of IVC stent-placements are rare and have been associated with complications and reinterventions [18]. Because a subset of patients can be successfully treated by venoplasty, stent placement should be reserved for patients with elastic recoiling stenosis, repeated recurrences after venoplasty, kinking related to graft position, torsion, or complete vessel obstruction [14]. Therefore, balloon angioplasty should be the primary procedure in the treatment of pediatric patients with these venous complications. Nevertheless, as our data suggest, balloon angioplasty can always be combined with stent placement in the same or in repeat interventions in case of balloon dilation failure. Hepatic Artery Most hepatic artery stenoses arise directly at the anastomosis within 3 months after liver transplantation. Early hepatic artery thrombosis is frequent after PLT. Early diagnosis is important to prevent secondary ischaemic biliary and parenchymal damage, which is associated with high rates of graft loss and mortality [19]. Long-term patency could be achieved in two of our patients with stenoses of the hepatic artery, which occurred as early as 3 months after PLT. In one patient with elastic stenosis and another patient with occlusion after an asymptomatic period after balloon angioplasty, we placed oversized stents (40 % oversized diameter). Again, the stents were selected as short as possible to permit a suitable length of unstented vessel for hepatic artery anastomosis in case of necessary repeated LT. The number of published pediatric cases is limited. In adult patients after LT, a patency rate of 60–80 % at 1-year follow-up was reported [20]. In one case of early hepatic artery thrombosis, we were not able to catheterize the hepatic artery. Before radiological intervention, this patient underwent several surgical revisions of the hepatic artery and the portal vein. Immediately before radiological intervention, packing was performed because of diffuse bleeding; the hepatic artery could not be detected afterward. We were not able to detect the hepatic artery by angiography either: Extensive liver necrosis had already developed before radiological intervention. Because of the anatomical changes resulting from the multiple revisions, it was not possible to recanalize the occluded vessel. When trying to canalize the hepatic artery, a guidewire perforation occurred; however, probably due to pre-existing packing, no significant bleeding occurred. In another child, we were also not able to cross the lesion and to recanalize a dissection. Anatomical changes because of the third PLT due to hepatic artery occlusions, and thus a complicated patch reconstruction of the hepatic artery,
W. Uller et al.: Interventions After PLT
which was anastomosed with the aorta, may have been the reason. In one case of early hepatic artery thrombosis, the thrombus could only be partially lysed by direct intrathrombotic application of urokinase in bolus form and as a continuous infusion. Additional heparin was infused. The simultaneous presence of stenotic segments distal to the anastomosis and multiple spasms of the segment arteries could have been the reasons for lysis failure. Long-term follow-up data for percutaneous revascularization of the hepatic artery are not yet available, and there are few reports of endovascular treatment [21, 22]. Hidalgo et al. [23] achieved good results by using urokinase in two patients with hepatic artery thrombosis immediately after liver transplantation, but both patients required PTA during follow-up. The results of these studies indicated the preferred use of urokinase as a thrombolytic agent and recommended the use of heparin to maintain the partial thromboplastin time between 1.5 and 2.5 times the control value [24]. Clinical safety and efficacy have been shown with different dosing regimes, but the lowest effective dosage and duration has not yet been determined. Discussed factors related to dosage are delineation of flow velocity, improvement in laboratory and clinical parameters or manifestation of any sign of complications [24]. There is no consensus on the ideal technique for catheterdirected delivery of any thrombolytic agent; continuous infusion and bolus have both been successfully used [25]. Nevertheless, selective thrombolysis by way of the hepatic artery has several advantages, such as decreased total thrombotic dose, high local concentration, and decreased influence on the systemic coagulation. Furthermore thrombolytic therapy seems to be safer and more effective if the infusion catheter is placed in the thrombus [26]. Our data suggest that, probably because of multiple surgical revisions and repeated PLT, it can be impossible in some cases to catheterize the hepatic artery, especially in case of dissection or occlusions after bleeding. Interventional radiological treatment of vascular complications after PLT is effective and safe, but general anesthesia or monitored anesthesia is mandatory. If repeated angioplasties of a vascular stenosis fail, stent placement can serve as an alternative, but this should be reserved for special cases due to possible mismatch of the diameter of the vessels and stents as well as graft and patient growth. We recommend selecting a stent of large diameter (40 % oversizing) and shortest possible length to achieve resolution of the stenosis and to consider the future growth of the child and the possibility of repeated dilations of the stent or retransplantation. The complex anatomic variations after PLT must be kept in mind, especially after repeated PLT and after surgical revisions of the vessels. The most appropriate access route must be chosen, taking
into consideration not only the needed material for angioplasty or the angle of the stenosed vessel, but also the vessel diameter chosen for access to avoid complications. In one case, temporary partial thrombosis of the external iliac artery occurred in a 8-month-old child when a 5F introducer sheath was used due to an angulated stenosed vessel. Thus, device sizes should be selected as small as possible to avoid complications due to mismatch of the size of the introducer sheaths and small access vessels that are prone to vasospasm. Therefore, for each patient a customized treatment plan with an individualized concept is necessary. An interdisciplinary discussion presenting therapeutic options for each patient should take place before treatment. Because the number of PLTs is limited and the technical options for the treatment of vascular complications are manifold, realization of a prospective randomized study is hardly feasible. Thus, this consecutive series of a small patient population is important and describes the variety, characteristics, and individuality of interventional management of all kinds of possible vascular stenosis or occlusions after PLT. Acknowledgments We thank Florian Full for critical reading of the manuscript and Dietlinde Ulsperger for help with figure preparation. Conflict of interest The authors Wibke Uller, Birgit Knoppke, Andreas G. Schreyer, Peter Heiss, Hans J. Schlitt, Michael Melter, Christian Stroszczynski, Niels Zorger and Walter A. Wohlgemuth declare no conflict of interest related to this publication
References 1. Beaunoyer M, Vanatta JM, Ogihara M et al (2007) Outcomes of transplantation in children with primary hepatic malignancy. Pediatr Transplant 11(6):655–660 2. Goss JA, Shackleton CR, McDiarmid SV et al (1998) Long-term results of pediatric liver transplantation: an analysis of 569 transplants. Ann Surg 228(3):411–420 3. Jain A, Mazariegos G, Kashyap R et al (2002) Pediatric liver transplantation. A single center experience spanning 20 years. Transplantation 73(6):941–947 4. Broelsch CE, Emond JC, Whitington PF, et al. (1990) Application of reduced-size liver transplants as split grafts, auxiliary orthotopic grafts, and living related segmental transplants. Ann Surg 212(3):368–375; discussion 375–367 5. Broelsch CE, Whitington PF, Emond JC, et al. (1991) Liver transplantation in children from living related donors. Surgical techniques and results. Ann Surg 214(4):428–437; discussion 437–429 6. Kalayoglu M, D’Alessandro AM, Knechtle SJ, et al. (1993) Long-term results of liver transplantation for biliary atresia. Surgery 114(4):711–717; discussion 717–718 7. Langnas AN, Marujo W, Stratta RJ, et al. (1991) Vascular complications after orthotopic liver transplantation. Am J Surg 161(1):76–82; discussion 82–73 8. Sieders E, Peeters PM, TenVergert EM et al (2000) Early vascular complications after pediatric liver transplantation. Liver Transpl 6(3):326–332
123
W. Uller et al.: Interventions After PLT 9. Ueda M, Egawa H, Ogawa K et al (2005) Portal vein complications in the long-term course after pediatric living donor liver transplantation. Transplant Proc 37(2):1138–1140 10. Buell JF, Funaki B, Cronin DC et al (2002) Long-term venous complications after full-size and segmental pediatric liver transplantation. Ann Surg 236(5):658–666 11. Abad J, Hidalgo EG, Cantarero JM et al (1989) Hepatic artery anastomotic stenosis after transplantation: treatment with percutaneous transluminal angioplasty. Radiology 171(3):661–662 12. Carnevale FC, Borges MV, Pinto RA et al (2004) Endovascular treatment of stenosis between hepatic vein and inferior vena cava following liver transplantation in a child: a case report. Pediatr Transplant 8(6):576–580 13. Kubo T, Shibata T, Itoh K et al (2006) Outcome of percutaneous transhepatic venoplasty for hepatic venous outflow obstruction after living donor liver transplantation. Radiology 239(1): 285–290 14. Lorenz JM, Van Ha T, Funaki B et al (2006) Percutaneous treatment of venous outflow obstruction in pediatric liver transplants. J Vasc Interv Radiol 17(11 Pt 1):1753–1761 15. Bertram H, Pfister E-D, Becker T et al (2010) Transsplenic endovascular therapy of portal vein stenosis and subsequent complete portal vein thrombosis in a 2-year-old child. J Vasc Interv Radiol 21(11):1760–1764 16. Carnevale FC, de Tarso Machado A, Moreira AM et al (2011) Long-term results of the percutaneous transhepatic venoplasty of portal vein stenoses after pediatric liver transplantation. Pediatr Transplant 15(1):476–481 17. Funaki B, Rosenblum JD, Leef JA et al (2000) Percutaneous treatment of portal venous stenosis in children and adolescents with segmental hepatic transplants: long-term results. Radiology 215(1):147–151
123
18. Carnevale FC, Machado AT, Moreira AM et al (2008) Midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation. J Vasc Interv Radiol 19(10):1439–1448 19. Stringer MD, Marshall MM, Muiesan P et al (2001) Survival and outcome after hepatic artery thrombosis complicating pediatric liver transplantation. J Pediatr Surg 36(6):888–891 20. Saad WE, Davies MG, Sahler L et al (2005) Hepatic artery stenosis in liver transplant recipients: primary treatment with percutaneous transluminal angioplasty. J Vasc Interv Radiol 16(6): 795–805 21. Hasegawa T, Sasaki T, Kimura T et al (2002) Successful percutaneous transluminal angioplasty for hepatic artery stenosis in an infant undergoing living-related liver transplantation. Pediatr Transplant 6(3):244–248 22. Lopez-Benitez R, Schlieter M, Hallscheidt PJ et al (2008) Successful arterial thrombolysis and percutaneous transluminal angioplasty for early hepatic artery thrombosis after split liver transplantation in a four-month-old baby. Pediatr Transplant 12(5):606–610 23. Hidalgo EG, Abad J, Cantarero JM et al (1989) High-dose intraarterial urokinase for the treatment of hepatic artery thrombosis in liver transplantation. Hepatogastroenterology 36(6):529–532 24. Singhal A, Stokes K, Sebastian A et al (2010) Endovascular treatment of hepatic artery thrombosis following liver transplantation. Transpl Int 23(3):245–256 25. Semba CP, Bakal CW, Calis KA et al (2000) Alteplase as an alternative to urokinase. Advisory panel on catheter-directed thrombolytic therapy. J Vasc Interv Radiol 11(3):279–287 26. Figueras J, Busquets J, Dominguez J et al (1995) Intra-arterial thrombolysis in the treatment of acute hepatic artery thrombosis after liver transplantation. Transplantation 59(9):1356–1357
