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Liver retransplantation in children in Poland
Liver Retransplantation in Children in Poland D. Broniszczak, A. Kaminski, P. Kalicinski, M. Szymczak, H. Ismail, T. Drewniak, P. Nachulewicz, M. Markiewicz, and J. Teisseyre ABSTRACT An average of 15% of patients require retransplantation due to irreversible liver graft failure due to primary graft nonfunction, chronic rejection, vascular and biliary complications, or infections. The survival of patients and grafts after retransplantation is inferior to that after primary transplantation. The purpose of the present study was to examine the incidence, indications, and outcome of retransplantation in children. In our center 169 liver transplantations had been performed in 154 patients, and 14 patients (9%) required 15 retransplantations: nine in the early postoperative period, five late after primary transplantation, and one late after the second transplantation. One-year patient survival after primary transplantation was 82%, but after early retransplantation it was 55%.
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IVER TRANSPLANTATION is the preferred treatment for patients with end-stage liver disease or fulminant liver failure. An average of 15% of patients require retransplantation (reTx) due to irreversible graft failure due to primary graft nonfunction (PNF), chronic rejection and vascular or biliary complications.1–3 The survival of patients and grafts after retransplantation is lower than after primary transplantation.2,4 The aim of this study was to examine indications for and outcome of retransplantation in children. MATERIALS AND METHODS In the period between March 1990 and April 2003, 169 transplantations were performed in 154 patients (121 cadaveric, 42 living related, six combined liver and kidney, one combined bowel and liver). Among these cases 14 patients (9%) required 15 retransplantations. In nine cases the intervention was required early, seven, within 3 to 10 days and 2, on posttransplant days 52 and 64. Late retransplantations were performed in six patients from 8 months to 8 years after primary transplantation. The indications for early reTx were PNF (n ⫽ 4) artery thrombosis (HAT) (n ⫽ 2) and graft compression (n ⫽ 3), namely two mismatched graft/recipient sizes, one case of hypoperfusion, and one case of portal vein thrombosis. In one patient HAT led to liver abscess, sepsis, and multiorgan failure (MOF). In another patient in addition to HAT were a relatively small graft (0.86% of body mass), sepsis, and MOF. Late reTx were caused by biliary complications (n ⫽ 4) chronic CMV infection (n ⫽ 1), and chronic rejection (n ⫽ 2) including one patient who also had biliary complications, while the other, noncompliance. Four retransplant patients received primary graft from a living related donor. We analyzed the rate of and patient survival and causes of mortality after early retransplantation.
RESULTS
One-year patient survival after primary transplantation in our center was 82%, 55% among nine patients with early retransplantation. Among six patients with late retransplantation, one died due to MOF. Follow-up in this group is too short to assess 1-year survival after retransplantation, however, 83% of patients are living at 3 to 17 months. The total incidence of retransplantation in our group was 9%; however, seven patients (14%) were among the first 50 recipients, including 6/7 early graft failures. Only eight reTx (7%) occured in the next 104 patients; five of these eight patients were very late from retransplants, suggesting a learning curve of our center. Causes of mortality after early retransplantation were: sepsis and MOF in four cases, central nervous system lesions in one case, and MOF in one patient after late retransplantation. DISCUSSION
Liver retransplantation is the only treatment when a primary graft fails. The majority of authors have reported retransplantation rates of 13% to 27.7% in children, which is generally higher than that in adults.1–3 Our 9% retransplantation rate was relatively low, comparing favorably with these reports from the pediatric population. At the beginFrom the Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, Warsaw, Poland. Address reprint requests to Dorota Broniszczak, Department of Pediatric Surgery, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04 –736 Warsaw, Poland.
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00803-0
Transplantation Proceedings, 35, 2271–2272 (2003)
2271
2272
ning of our experience it was higher (14%), but with time it decreased to 7%, which was attributed to a reduced incidence of PNF in our patients (8% in the first 50 patients vs ⬍1% in the next 104 patients). Apart from gaining experience, during the same period we changed our protocol from perform histopathological examination of all harvested grafts before making a decision to implant them to proceeds without awaiting a pathology report based upon macroscopic features of the donor liver. This change reduced mean cold ischemia time from almost 15 hours to less than 10 hours, and PNF became almost nonexistent. Hepatic artery thrombosis is a catastrophic event after liver transplantation, usually treated too late, and unsuccessful thrombectomy, which requires prompt retransplantation.5 In small pediatric recipients receiving relatively large grafts, high intraabdominal pressure increases the risk of hepatic artery and portal vein thrombosis, which occurred in one of our patients. Size mismatch, swelling of the graft, and premature abdominal closure in two patients led to sudden graft failure and necrosis despite good vascular flow on ultrasound Doppler examination. Delayed abdominal wall closure or only skin closure should be performed in all cases with size mismatches, while full layer closure is defined for several months. The main indication for elective retransplantation in our group was nonischemic biliary complications such as multiple billary structures, reccurrent cholangitis etc, leading to secondary biliary cirrhosis or intractable sepsis. In a large series late liver retransplantations in children were mostly performed due to infections or chronic rejection, followed by biliary complications.6 In our series biliary problems and
BRONISZCZAK, KAMINSKI, KALICINSKI ET AL
related infectious complications led to the majority of late retransplants. Most reports show that patient and graft survival rates are inferior after reTx than after the first graft.2,4 Also proven the mortality rate after primary transplants for urgent indications is higher than that in elective patients. The same observations concern survival rates after emergent or elective retransplantations.7 Our study confirms these observations. One-year patient survival after primary transplantation in our experience was 82% vs 55% after emergency retransplantation. This difference is obviously the consequence of the urgent status of patients listed for retransplantation, acceptance of marginal donors and ABO incompatibility in some instances. In six electively retransplanted patients the follow-up period was longer than 1 year including one death. Another two cases were retransplanted recently and both are alive with a follow-up of 2 months and a good prognosis for long-term survival. REFERENCES 1. Hamada H, Valayer J, Gauthier F, et al: J Pediatr Surg 30:705, 1995 2. Deshapande RR, Rela M, Girlanda R, et al: Transplantation 74:1124, 2002 3. Newell KA, Alonso EM, Millis JM, et al: Transplant Proc 29:442, 1997 4. Sieders E, Peeters PM, Ten Vergert EM, et al: Transplantation 71:90, 2001 5. Garcia-Gallont R, Bar-Nathan N, Shaharabani E, et al: Pediatr Transplant 3:78, 1999 6. Wallot MA, Mathot M, Janssen M, et al: Liver Transplant 87:615, 2002 7. Kumar N, Wall WJ, Grant DR, et al: Transplant Proc 31:541, 1999
L
IVER TRANSPLANTATION is the preferred treatment for patients with end-stage liver disease or fulminant liver failure. An average of 15% of patients require retransplantation (reTx) due to irreversible graft failure due to primary graft nonfunction (PNF), chronic rejection and vascular or biliary complications.1–3 The survival of patients and grafts after retransplantation is lower than after primary transplantation.2,4 The aim of this study was to examine indications for and outcome of retransplantation in children. MATERIALS AND METHODS In the period between March 1990 and April 2003, 169 transplantations were performed in 154 patients (121 cadaveric, 42 living related, six combined liver and kidney, one combined bowel and liver). Among these cases 14 patients (9%) required 15 retransplantations. In nine cases the intervention was required early, seven, within 3 to 10 days and 2, on posttransplant days 52 and 64. Late retransplantations were performed in six patients from 8 months to 8 years after primary transplantation. The indications for early reTx were PNF (n ⫽ 4) artery thrombosis (HAT) (n ⫽ 2) and graft compression (n ⫽ 3), namely two mismatched graft/recipient sizes, one case of hypoperfusion, and one case of portal vein thrombosis. In one patient HAT led to liver abscess, sepsis, and multiorgan failure (MOF). In another patient in addition to HAT were a relatively small graft (0.86% of body mass), sepsis, and MOF. Late reTx were caused by biliary complications (n ⫽ 4) chronic CMV infection (n ⫽ 1), and chronic rejection (n ⫽ 2) including one patient who also had biliary complications, while the other, noncompliance. Four retransplant patients received primary graft from a living related donor. We analyzed the rate of and patient survival and causes of mortality after early retransplantation.
RESULTS
One-year patient survival after primary transplantation in our center was 82%, 55% among nine patients with early retransplantation. Among six patients with late retransplantation, one died due to MOF. Follow-up in this group is too short to assess 1-year survival after retransplantation, however, 83% of patients are living at 3 to 17 months. The total incidence of retransplantation in our group was 9%; however, seven patients (14%) were among the first 50 recipients, including 6/7 early graft failures. Only eight reTx (7%) occured in the next 104 patients; five of these eight patients were very late from retransplants, suggesting a learning curve of our center. Causes of mortality after early retransplantation were: sepsis and MOF in four cases, central nervous system lesions in one case, and MOF in one patient after late retransplantation. DISCUSSION
Liver retransplantation is the only treatment when a primary graft fails. The majority of authors have reported retransplantation rates of 13% to 27.7% in children, which is generally higher than that in adults.1–3 Our 9% retransplantation rate was relatively low, comparing favorably with these reports from the pediatric population. At the beginFrom the Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, Warsaw, Poland. Address reprint requests to Dorota Broniszczak, Department of Pediatric Surgery, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04 –736 Warsaw, Poland.
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00803-0
Transplantation Proceedings, 35, 2271–2272 (2003)
2271
2272
ning of our experience it was higher (14%), but with time it decreased to 7%, which was attributed to a reduced incidence of PNF in our patients (8% in the first 50 patients vs ⬍1% in the next 104 patients). Apart from gaining experience, during the same period we changed our protocol from perform histopathological examination of all harvested grafts before making a decision to implant them to proceeds without awaiting a pathology report based upon macroscopic features of the donor liver. This change reduced mean cold ischemia time from almost 15 hours to less than 10 hours, and PNF became almost nonexistent. Hepatic artery thrombosis is a catastrophic event after liver transplantation, usually treated too late, and unsuccessful thrombectomy, which requires prompt retransplantation.5 In small pediatric recipients receiving relatively large grafts, high intraabdominal pressure increases the risk of hepatic artery and portal vein thrombosis, which occurred in one of our patients. Size mismatch, swelling of the graft, and premature abdominal closure in two patients led to sudden graft failure and necrosis despite good vascular flow on ultrasound Doppler examination. Delayed abdominal wall closure or only skin closure should be performed in all cases with size mismatches, while full layer closure is defined for several months. The main indication for elective retransplantation in our group was nonischemic biliary complications such as multiple billary structures, reccurrent cholangitis etc, leading to secondary biliary cirrhosis or intractable sepsis. In a large series late liver retransplantations in children were mostly performed due to infections or chronic rejection, followed by biliary complications.6 In our series biliary problems and
BRONISZCZAK, KAMINSKI, KALICINSKI ET AL
related infectious complications led to the majority of late retransplants. Most reports show that patient and graft survival rates are inferior after reTx than after the first graft.2,4 Also proven the mortality rate after primary transplants for urgent indications is higher than that in elective patients. The same observations concern survival rates after emergent or elective retransplantations.7 Our study confirms these observations. One-year patient survival after primary transplantation in our experience was 82% vs 55% after emergency retransplantation. This difference is obviously the consequence of the urgent status of patients listed for retransplantation, acceptance of marginal donors and ABO incompatibility in some instances. In six electively retransplanted patients the follow-up period was longer than 1 year including one death. Another two cases were retransplanted recently and both are alive with a follow-up of 2 months and a good prognosis for long-term survival. REFERENCES 1. Hamada H, Valayer J, Gauthier F, et al: J Pediatr Surg 30:705, 1995 2. Deshapande RR, Rela M, Girlanda R, et al: Transplantation 74:1124, 2002 3. Newell KA, Alonso EM, Millis JM, et al: Transplant Proc 29:442, 1997 4. Sieders E, Peeters PM, Ten Vergert EM, et al: Transplantation 71:90, 2001 5. Garcia-Gallont R, Bar-Nathan N, Shaharabani E, et al: Pediatr Transplant 3:78, 1999 6. Wallot MA, Mathot M, Janssen M, et al: Liver Transplant 87:615, 2002 7. Kumar N, Wall WJ, Grant DR, et al: Transplant Proc 31:541, 1999