- Email: [email protected]
Stent Placement in Pediatric Patients With Hepatic Artery Stenosis or Thrombosis After Liver Transplantation
Stent Placement in Pediatric Patients With Hepatic Artery Stenosis or Thrombosis After Liver Transplantation F. Boyvat, C. Aytekin, H. Karakayalı, U. Özyer, S . Sevmis, R. Emirog˘lu, and M. Haberal ABSTRACT Hepatic artery stenosis (HAS) and thrombosis (HAT) after orthotopic liver transplantation remain significant causes of graft loss. Postoperative HAT follows approximately 5% to 19% of orthotopic liver transplantation. It is seen more frequently in pediatric patients. In the past, repeat transplantation was considered the first choice for therapy. Recently, interventional radiological techniques, such as thrombolysis, percutaneous transluminal angioplasty, or stent placement in the hepatic artery, have been suggested, but little data exist related to stent placement in the thrombosed hepatic artery during the early postoperative period in pediatric patients. Between March 2000 and March 2005, percutaneous endoluminal stent placement was performed in seven pediatric liver transplant patients. HAT or HAS initially diagnosed in all cases by Doppler ultrasound then confirmed angiographically. We intervened in four cases of hepatic artery stenosis and three cases of hepatic artery occlusion. Stents were placed in all patients. Three ruptures were seen during percutaneous transluminal angioplasty of the hepatic artery using a covered coronary stents on the first, fifth day, or 17th postoperative day. In one patient, dissection of the origin of the common hepatic artery developed owing to a guiding sheath, and a second stent was placed to cover the dissected segment. The other two hepatic artery stents remained patent. In one stent became occluded at 3 months after the intervention with no clinical problems. Follow-up ranged from 9 to 40 months. In conclusion, early and late postoperative stent placement in the graft hepatic artery was technically feasible.
V
ASCULAR COMPLICATIONS, especially in the arterial tree following liver transplantation, are associated with a high incidence of morbidity and mortality. The incidence of hepatic artery thrombosis (HAT) varies from 2.6% to 20% in adults and as high as 30% in children younger than 1 year old.1–3 Hepatic artery stenosis (HAS) rates as high as 11% have been reported.4 HAS may follow an insidious course leading to graft dysfunction or biliary complications. However, HAT is a potentially life-threatening complication; the mortality is higher when HAT occurs shortly after liver transplantation. Patients with HAT within 4 postoperative weeks may present with acute graft failure, sepsis, liver abscess, biliary leak, or biliary stricture. The presentation of delayed HAT is variable.5 Treatment of early HAT usually requires surgical intervention, with retransplantation or surgical revascularization. However, retransplantation is limited by organ availability and patient condition.6 Interventional radiology plays a major role in the treatment of vascular complications after liver transplantation by per-
forming percutaneous transluminal angioplasty (PTA) or stent placement. In this study, we have presented our endovascular stent experience in the management of HAS and HAT following pediatric liver transplantation. MATERIALS AND METHODS Between March 2000 and March 2005, percutaneous endoluminal stent placements were performed in seven pediatric liver transplant patients (two girls, five boys; mean age, 10.8 years; range, 5 to 16 years). HAT or HAS was initially diagnosed in all cases with Doppler ultrasound and then confirmed angiographically. After selective catheterization of the hepatic artery, a microcatheter and a 0.016-inch guide wire was negotiated and advanced to the distal From the Department of Radiology and General Surgery, Baskent University, Ankara, Turkey. Address reprint requests to Prof Mehmet Haberal, MD, FACS, FICS (Hon), Department of General Surgery, Baskent University, 1 Cadde No 77 Kat 4, Bahcelievler, Ankara 6490, Turkey. E-mail: [email protected]
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.10.169
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3656
Transplantation Proceedings, 38, 3656 –3660 (2006)
STENT PLACEMENT IN PEDIATRIC PATIENTS
3657
Table 1. Summary of Patients and Prognosis Patient No.
Age/Sex
Graft
1 2 3 4 5 6 7
14/F 10/M 16/M 13/F 9/M 8/M 4/M
LA ⫹ Ca LA LL RL LA Whole LA
Presentation
HAS HAS HAS HAT HAS HAT HAT
Postop Days of Int
No. of Int
Follow-up of HA
Outcome (post int)
180 d 17 d 18 d 1d 1d 1d 5d
1 1 2 2 1 1 2
Patent (50 mo) Patent (40 mo) Patent (3 mo) Occluded (3 mo) Patent (17 mo) Patent (2 days) Patent (9 mo)
Alive (50 mo) Alive (40 mo) Death (3 mo) Alive (19 mo) Alive (17 mo) Death (2 days) Alive (9 mo)
(90%) (80%) (90%) (90%)
Abbreviations: LA, lateral lobe; Ca, caudate; LL, left lobe; RL, right lobe; HA, hepatic artery; HAS, hepatic artery stenosis; HAT, hepatic artery thrombosis; int, intervention; Op, operative.
hepatic artery. A 0.014-inch stiff guide wire was placed through the microcatheter, and the remaining procedure was accomplished through this guide wire. A 6-French guiding catheter was advanced to the celiac trunk. If the patient had HAT, local thrombolysis was performed with a dose of 100,000 to 250,000 U urokinase or 1 to 3 mg tPA. Later, PTA and stent placement were performed as percutaneous interventions in four hepatic artery stenoses and three hepatic artery occlusions. The wall-stents (Boston Scientific), coronary stents (Boston Scientific), or graft-covered stents (jo stent, Abbott Vascular Devices, Netherland; over and under; Medical Ventures Corp, Canada) were used for the procedures. Stents were placed on the first day (n ⫽ 3), the fifth day (n ⫽ 1), the 17th day (n ⫽ 1), the 18th day (n ⫽ 1), and the 180th day (n ⫽ 1) postoperatively. The patient data are summarized in Table 1.
RESULTS
Stents were placed in the hepatic arteries either for restenosis of more than 20% in diameter after PTA (Fig 1), for dissection, or for extravasation of contrast. In two patients, wall stents were deployed. In the remaining five patients, we used coronary stents (graft-covered stents in three patients). The technical success rate was 100%. Three ruptures were seen during PTA of the hepatic artery on the first, fifth, and 17th postoperative days of intervention; graftcovered coronary stents were placed with no major complications. In one patient, during stent placement dissection of the origin of the common hepatic artery developed owing to the guiding sheath, and a second stent was placed proximally to cover the dissected segment. During follow-up three patients, had early thrombosis of the hepatic artery diagnosed by Doppler ultrasound requiring second interventions. During the second intervention of the seventh patient because of a thrombosed hepatic artery, a microcatheter was left in the hepatic artery for 2 days for continuous thrombolysis (Table 1). Thereafter, good flow was established. The other two hepatic artery stents remained patent. One of the patients had a hepatic stent that occluded 3 months after the intervention with no clinical problems. The third patient died 3 months after stent placement owing to multiorgan failure. The hepatic stent was patent at the time of death. Follow-up ranged from 9 to 40 months.
DISCUSSION
Hepatic artery stenosis has been reported to occur in 2% to 13% of cases.7 The etiology of HAS may be due to operative technique or vascular clamp injury, allograft rejection, preservation injury, anastomosis of the small arteries, or procoagulant disorders.8 Stenoses have been found to occur at the anastomotic site in 70% of cases.7 HAS may be undetected and cause insidious and persistent ischemic effects to the graft. Initially it causes uncomplicated and reversible biliary ischemia; later it causes irreversible biliary necrosis, which leads to allograft dysfunction. Therefore, early detection and treatment of HAS are critical for good graft survival. Although HAS after liver transplantation is treated by either surgical repair or retransplantation, interventional radiological procedures such as PTA or stents recently have been reported with good outcomes. In a study by Denys and colleagues,9 13 hepatic arteries with stenosis were stented with only one stent becoming thrombosed. In another report, stents were placed in four patients with good outcomes.10 In our series, four patients with hepatic artery stenoses were treated with bare or graft-covered stents. The reasons for stent placement in these patients were one rupture in patient number 2 and an ineffective PTA in three patients, namely, restenosis more than 20% after PTA or dissection. Without emergent retransplantation or revascularization, mortality rates from HAT have been reported to be greater than 80%.1 The risk of HAT after transplantation has been associated with several factors such as multiple transplants, recipient/donor weight ratio ⬎ 1.25, ABO incompatibility, technical complications during reconstruction, acute rejection, long cold ischemia times, and cytomegalovirus infection.11,12 When HAT is diagnosed rapid revascularization is essential. Retransplantation is the treatment of choice but not always possible owing to the organ shortage. However, even after retransplantation for early HAT, survival rates range from 30% to 50%.13 Recently, endovascular interventions have been successfully applied to treat complications of transplantation. There is no agreement about the time of PTA or stent placement to hepatic arteries after transplantation. Early intervention of fresh hepatic artery anastomo-
3658
BOYVAT, AYTEKIN, KARAKAYALI ET AL
Fig 1. A 9-year-old boy, first postoperative day. (A) Angiography revealed 90% stenosis of the hepatic artery (arrow). (B) After unsatisfactory PTA with 3-mm balloon. (C) Stent was placed with good result. (D) One year later, angiography control showed patent hepatic artery without stenosis.
ses may lead to rupture. For endovascular interventions of hepatic arteries, some authors suggest waiting at least 7 days postoperatively to prevent rupture of the artery while
some suggest 3 weeks.7,14 In our series, interventions were performed during the early postoperative period. In two patients with HAT, we observed extravasation of the con-
STENT PLACEMENT IN PEDIATRIC PATIENTS
3659
Fig 2. An 8-year-old patient, first postoperative day. (A) Selective celiac arteriography demonstrated occluded hepatic artery (arrows). (B) Selective catheterization followed by thrombolysis and PTA revealed flow of the hepatic artery with rupture. (C) Graft-covered stents were placed to seal and keep the vessel open.
trast and intra-abdominal bleeding but these were treated with graft covered coronary stents (Fig 2). These graft-covered stents were lifesaving tools for the patient. Percutaneous endovascular interventions can be performed even on the first day after transplantation. We have even applied continuous thrombolysis to lyse residual thrombus inside distal hepatic artery branches after graft-covered stent placement. In conclusion, percutaneous endovascular stent placement is an effective treatment for HAS or HAT after pediatric liver transplantation. Graft-covered stents are effective for treatment of early hepatic arterial complications.
REFERENCES 1. Amesur NB, Zajko AB: Interventional radiology in liver transplantation. Liver Transpl 12:330, 2006 2. Oh CK, Pelletier SJ, Sawyer RG, et al: Uni- and multi-variate analysis of risk factors for early and late hepatic artery thrombosis after liver transplantation. Transplantation 71:767, 2001 3. Heffron TG, Pillen T, Welch D, et al: Hepatic artery thrombosis in pediatric liver transplantation. Transplant Proc 35:1447, 2003 4. Vignali C, Bargellini I, Cioni R, et al: Diagnosis and treatment of hepatic artery stenosis after orthotopic liver transplantation. Transplant Proc 36:2771, 2004
3660 5. Stange BJ, Glanemann M, Nuessler NC, et al: Hepatic artery thrombosis after adult liver transplantation. Liver Transpl 9:612, 2003 6. Tian MG, Tso WK, Lo CM, et al: Treatment of hepatic artery thrombosis after orthotopic liver transplantation. Asian J Surg 27:213, 2004 (discussion 218) 7. Kodama Y, Sakuhara Y, Abo D, et al: Percutaneous transluminal angioplasty for hepatic artery stenosis after living donor liver transplantation. Liver Transpl 12:465, 2006 8. Karani JB, Yu DF, Kane PA: Interventional radiology in liver transplantation. Cardiovasc Intervent Radiol 28:271, 2005 9. Denys AL, Qanadli SD, Durand F, et al: Feasibility and effectiveness of using coronary stents in the treatment of hepatic artery stenoses after orthotopic liver transplantation: preliminary report. AJR Am J Roentgenol 178:1175, 2002
BOYVAT, AYTEKIN, KARAKAYALI ET AL 10. Cotroneo AR, Di Stasi C, Cina A, et al: Stent placement in four patients with hepatic artery stenosis or thrombosis after liver transplantation. J Vasc Interv Radiol 13:619, 2002 11. Zhou J, Fan J, Wang JH, et al: Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation. Transplant Proc 37:4426, 2005 12. Settmacher U, Stange B, Haase R, et al: Arterial complications after liver transplantation. Transpl Int 13:372, 2000 13. Massault PP, Soubrane O, Cardoso J, et al: Graft saving management of hepatic artery thrombosis in pediatric liver transplantation. Transplant Proc 29:439, 1997 14. Ueno T, Jones G, Martin A, et al: Clinical outcomes from hepatic artery stenting in liver transplantation. Liver Transpl 12:422, 2006
V
ASCULAR COMPLICATIONS, especially in the arterial tree following liver transplantation, are associated with a high incidence of morbidity and mortality. The incidence of hepatic artery thrombosis (HAT) varies from 2.6% to 20% in adults and as high as 30% in children younger than 1 year old.1–3 Hepatic artery stenosis (HAS) rates as high as 11% have been reported.4 HAS may follow an insidious course leading to graft dysfunction or biliary complications. However, HAT is a potentially life-threatening complication; the mortality is higher when HAT occurs shortly after liver transplantation. Patients with HAT within 4 postoperative weeks may present with acute graft failure, sepsis, liver abscess, biliary leak, or biliary stricture. The presentation of delayed HAT is variable.5 Treatment of early HAT usually requires surgical intervention, with retransplantation or surgical revascularization. However, retransplantation is limited by organ availability and patient condition.6 Interventional radiology plays a major role in the treatment of vascular complications after liver transplantation by per-
forming percutaneous transluminal angioplasty (PTA) or stent placement. In this study, we have presented our endovascular stent experience in the management of HAS and HAT following pediatric liver transplantation. MATERIALS AND METHODS Between March 2000 and March 2005, percutaneous endoluminal stent placements were performed in seven pediatric liver transplant patients (two girls, five boys; mean age, 10.8 years; range, 5 to 16 years). HAT or HAS was initially diagnosed in all cases with Doppler ultrasound and then confirmed angiographically. After selective catheterization of the hepatic artery, a microcatheter and a 0.016-inch guide wire was negotiated and advanced to the distal From the Department of Radiology and General Surgery, Baskent University, Ankara, Turkey. Address reprint requests to Prof Mehmet Haberal, MD, FACS, FICS (Hon), Department of General Surgery, Baskent University, 1 Cadde No 77 Kat 4, Bahcelievler, Ankara 6490, Turkey. E-mail: [email protected]
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.10.169
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3656
Transplantation Proceedings, 38, 3656 –3660 (2006)
STENT PLACEMENT IN PEDIATRIC PATIENTS
3657
Table 1. Summary of Patients and Prognosis Patient No.
Age/Sex
Graft
1 2 3 4 5 6 7
14/F 10/M 16/M 13/F 9/M 8/M 4/M
LA ⫹ Ca LA LL RL LA Whole LA
Presentation
HAS HAS HAS HAT HAS HAT HAT
Postop Days of Int
No. of Int
Follow-up of HA
Outcome (post int)
180 d 17 d 18 d 1d 1d 1d 5d
1 1 2 2 1 1 2
Patent (50 mo) Patent (40 mo) Patent (3 mo) Occluded (3 mo) Patent (17 mo) Patent (2 days) Patent (9 mo)
Alive (50 mo) Alive (40 mo) Death (3 mo) Alive (19 mo) Alive (17 mo) Death (2 days) Alive (9 mo)
(90%) (80%) (90%) (90%)
Abbreviations: LA, lateral lobe; Ca, caudate; LL, left lobe; RL, right lobe; HA, hepatic artery; HAS, hepatic artery stenosis; HAT, hepatic artery thrombosis; int, intervention; Op, operative.
hepatic artery. A 0.014-inch stiff guide wire was placed through the microcatheter, and the remaining procedure was accomplished through this guide wire. A 6-French guiding catheter was advanced to the celiac trunk. If the patient had HAT, local thrombolysis was performed with a dose of 100,000 to 250,000 U urokinase or 1 to 3 mg tPA. Later, PTA and stent placement were performed as percutaneous interventions in four hepatic artery stenoses and three hepatic artery occlusions. The wall-stents (Boston Scientific), coronary stents (Boston Scientific), or graft-covered stents (jo stent, Abbott Vascular Devices, Netherland; over and under; Medical Ventures Corp, Canada) were used for the procedures. Stents were placed on the first day (n ⫽ 3), the fifth day (n ⫽ 1), the 17th day (n ⫽ 1), the 18th day (n ⫽ 1), and the 180th day (n ⫽ 1) postoperatively. The patient data are summarized in Table 1.
RESULTS
Stents were placed in the hepatic arteries either for restenosis of more than 20% in diameter after PTA (Fig 1), for dissection, or for extravasation of contrast. In two patients, wall stents were deployed. In the remaining five patients, we used coronary stents (graft-covered stents in three patients). The technical success rate was 100%. Three ruptures were seen during PTA of the hepatic artery on the first, fifth, and 17th postoperative days of intervention; graftcovered coronary stents were placed with no major complications. In one patient, during stent placement dissection of the origin of the common hepatic artery developed owing to the guiding sheath, and a second stent was placed proximally to cover the dissected segment. During follow-up three patients, had early thrombosis of the hepatic artery diagnosed by Doppler ultrasound requiring second interventions. During the second intervention of the seventh patient because of a thrombosed hepatic artery, a microcatheter was left in the hepatic artery for 2 days for continuous thrombolysis (Table 1). Thereafter, good flow was established. The other two hepatic artery stents remained patent. One of the patients had a hepatic stent that occluded 3 months after the intervention with no clinical problems. The third patient died 3 months after stent placement owing to multiorgan failure. The hepatic stent was patent at the time of death. Follow-up ranged from 9 to 40 months.
DISCUSSION
Hepatic artery stenosis has been reported to occur in 2% to 13% of cases.7 The etiology of HAS may be due to operative technique or vascular clamp injury, allograft rejection, preservation injury, anastomosis of the small arteries, or procoagulant disorders.8 Stenoses have been found to occur at the anastomotic site in 70% of cases.7 HAS may be undetected and cause insidious and persistent ischemic effects to the graft. Initially it causes uncomplicated and reversible biliary ischemia; later it causes irreversible biliary necrosis, which leads to allograft dysfunction. Therefore, early detection and treatment of HAS are critical for good graft survival. Although HAS after liver transplantation is treated by either surgical repair or retransplantation, interventional radiological procedures such as PTA or stents recently have been reported with good outcomes. In a study by Denys and colleagues,9 13 hepatic arteries with stenosis were stented with only one stent becoming thrombosed. In another report, stents were placed in four patients with good outcomes.10 In our series, four patients with hepatic artery stenoses were treated with bare or graft-covered stents. The reasons for stent placement in these patients were one rupture in patient number 2 and an ineffective PTA in three patients, namely, restenosis more than 20% after PTA or dissection. Without emergent retransplantation or revascularization, mortality rates from HAT have been reported to be greater than 80%.1 The risk of HAT after transplantation has been associated with several factors such as multiple transplants, recipient/donor weight ratio ⬎ 1.25, ABO incompatibility, technical complications during reconstruction, acute rejection, long cold ischemia times, and cytomegalovirus infection.11,12 When HAT is diagnosed rapid revascularization is essential. Retransplantation is the treatment of choice but not always possible owing to the organ shortage. However, even after retransplantation for early HAT, survival rates range from 30% to 50%.13 Recently, endovascular interventions have been successfully applied to treat complications of transplantation. There is no agreement about the time of PTA or stent placement to hepatic arteries after transplantation. Early intervention of fresh hepatic artery anastomo-
3658
BOYVAT, AYTEKIN, KARAKAYALI ET AL
Fig 1. A 9-year-old boy, first postoperative day. (A) Angiography revealed 90% stenosis of the hepatic artery (arrow). (B) After unsatisfactory PTA with 3-mm balloon. (C) Stent was placed with good result. (D) One year later, angiography control showed patent hepatic artery without stenosis.
ses may lead to rupture. For endovascular interventions of hepatic arteries, some authors suggest waiting at least 7 days postoperatively to prevent rupture of the artery while
some suggest 3 weeks.7,14 In our series, interventions were performed during the early postoperative period. In two patients with HAT, we observed extravasation of the con-
STENT PLACEMENT IN PEDIATRIC PATIENTS
3659
Fig 2. An 8-year-old patient, first postoperative day. (A) Selective celiac arteriography demonstrated occluded hepatic artery (arrows). (B) Selective catheterization followed by thrombolysis and PTA revealed flow of the hepatic artery with rupture. (C) Graft-covered stents were placed to seal and keep the vessel open.
trast and intra-abdominal bleeding but these were treated with graft covered coronary stents (Fig 2). These graft-covered stents were lifesaving tools for the patient. Percutaneous endovascular interventions can be performed even on the first day after transplantation. We have even applied continuous thrombolysis to lyse residual thrombus inside distal hepatic artery branches after graft-covered stent placement. In conclusion, percutaneous endovascular stent placement is an effective treatment for HAS or HAT after pediatric liver transplantation. Graft-covered stents are effective for treatment of early hepatic arterial complications.
REFERENCES 1. Amesur NB, Zajko AB: Interventional radiology in liver transplantation. Liver Transpl 12:330, 2006 2. Oh CK, Pelletier SJ, Sawyer RG, et al: Uni- and multi-variate analysis of risk factors for early and late hepatic artery thrombosis after liver transplantation. Transplantation 71:767, 2001 3. Heffron TG, Pillen T, Welch D, et al: Hepatic artery thrombosis in pediatric liver transplantation. Transplant Proc 35:1447, 2003 4. Vignali C, Bargellini I, Cioni R, et al: Diagnosis and treatment of hepatic artery stenosis after orthotopic liver transplantation. Transplant Proc 36:2771, 2004
3660 5. Stange BJ, Glanemann M, Nuessler NC, et al: Hepatic artery thrombosis after adult liver transplantation. Liver Transpl 9:612, 2003 6. Tian MG, Tso WK, Lo CM, et al: Treatment of hepatic artery thrombosis after orthotopic liver transplantation. Asian J Surg 27:213, 2004 (discussion 218) 7. Kodama Y, Sakuhara Y, Abo D, et al: Percutaneous transluminal angioplasty for hepatic artery stenosis after living donor liver transplantation. Liver Transpl 12:465, 2006 8. Karani JB, Yu DF, Kane PA: Interventional radiology in liver transplantation. Cardiovasc Intervent Radiol 28:271, 2005 9. Denys AL, Qanadli SD, Durand F, et al: Feasibility and effectiveness of using coronary stents in the treatment of hepatic artery stenoses after orthotopic liver transplantation: preliminary report. AJR Am J Roentgenol 178:1175, 2002
BOYVAT, AYTEKIN, KARAKAYALI ET AL 10. Cotroneo AR, Di Stasi C, Cina A, et al: Stent placement in four patients with hepatic artery stenosis or thrombosis after liver transplantation. J Vasc Interv Radiol 13:619, 2002 11. Zhou J, Fan J, Wang JH, et al: Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation. Transplant Proc 37:4426, 2005 12. Settmacher U, Stange B, Haase R, et al: Arterial complications after liver transplantation. Transpl Int 13:372, 2000 13. Massault PP, Soubrane O, Cardoso J, et al: Graft saving management of hepatic artery thrombosis in pediatric liver transplantation. Transplant Proc 29:439, 1997 14. Ueno T, Jones G, Martin A, et al: Clinical outcomes from hepatic artery stenting in liver transplantation. Liver Transpl 12:422, 2006