Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild.

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.

Preservation of the native spleen in multivisceral transplantation.

The native spleen is usually removed in patients undergoing MTV. The consequential asplenic state is associated with a high risk of sepsis, especially in immunosuppressed children. In contrast, the inclusion of an allogeneic spleen in multivisceral grafts has been associated with a high incidence of GVHD. We propose an alternative technique for patients undergoing MTV, consisting of the preservation of the native spleen. This approach avoids the additional risk of infection that characterizes the asplenic state without the detrimental side effects of the allogeneic spleen.

Liver transplantation in children with cystic fibrosis: experience in our centre and preliminary results with a combined en bloc liver-pancreas graft.

AIM OF THE STUDY: Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: (1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; (2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT). METHODS: 9 children (6M/3F) with CF and ESLD underwent LT between 1993 and 2010; median age and weight were 12.3 years (range: 5.4-17.0) and 36.7 kg (range: 14.2-58.5), respectively. 4 patients received a whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT. Immunosuppression followed the protocols at the time of transplantation. RESULTS: Liver function was restored in all patients and none of them needed re-transplantation. Median follow-up was 105 months (range: 4-206). 1 child died of respiratory failure at 23 months after transplantation while awaiting pulmonary transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children already had IDD before transplantation and 3 developed diabetes immediately after transplantation. 2 had not developed IDD at the end of the study: the youngest at the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and who recovered normal exocrine and endocrine pancreatic function after transplantation. CONCLUSIONS: LT is a realistic option to treat CF-related ESLD children. IDD is common in these patients. En bloc liver-pancreas transplantation is an appealing option, since it simultaneously restores exocrine function and prevents IDD. This procedure has clear technical advantages over simultaneous isolated liver and pancreas transplantation.

Necesidad de la bipartición hepática o split en el trasplante en niños / Need of hepatic bipartition or split in the transplant in children

Objetivo. Analizar el beneficio del trasplante hepático (TH) con labipartición adulto-niño. Pacientes /métodos. 1) Análisis de la mortalidad pretrasplante calculadas sobre 228 inclusiones a TH (enero 2004-diciembre 2008).2) Impacto de las técnicas alternativas (donante vivo/bipartición) en la mortalidad pretrasplante de nuestros enfermos. 3) Análisis de los resultados de 33 biparticiones que dieron lugar a 66 trasplantes (1994-2008). Resultados. Referida por 1.000 enfermos y año de exposición, la mortalidad pretrasplante fue de 110 en niños mayores de 5 años, 180en niños de 2 a 5 años, 90 en niños entre 1 y 2 años, y 510 en menores de 1 año (p<0,05 respecto a restantes grupos). 36/66 injertos divididos fueron implantados por nuestro grupo. Cinco se perdieron, 3 por retrasplante, 2 por fallecimiento. La supervivencia actuarial a 10 años fue94,5% (enfermos) y 85,1% (injerto). Los 30 injertos restantes fueron trasplantados en otros hospitales, de los que 4 se perdieron precozmente. En el (..) (AU)

Aim. To analyze the benefits of Split (for adult and for child) in liver transplantation. Patient/methods. 1) Analysis of the waiting list mortality estimated on 228 inclusions for transplant since January 2004 to December2008. 2) Impact of the variant techniques (living-related donor and split)on the waiting list mortality in our patients. 3) Analysis of the outcome of 33 split livers which allowed to perform 66 transplants (1994-2008). Results. Estimated as number of patients by 1,000 candidates by year of exposure, the waiting list mortality was 110 in children older than5 year old, 180 in children from 2 to 5 year-old, 90 in children between1 and 2 year-old and 510 in younger than 1 year (p<0.05 for the last group). 36/66 split grafts were implanted by our group. Five grafts were (..) (AU)

Trasplante intestinal: ¿en qué fase estamos? / Intestinal transplant: in what phase are we?

Objetivo. Analizar la evolución del trasplante intestinal (TI) desde el inicio del programa .Material y métodos. Estudiamos retrospectivamente todos los niños con TI (1997-2009): epidemiología, situación previa, técnica quirúrgica, inmunosupresión, resultados, supervivencia y calidad de vida .Resultados. Realizamos 52 TI (20 intestinal aislado, 20 hepatointestinal, 12 multiviscerales) en 46 niños, edad mediana 32m (rango7m-19a); peso 12,3 kg (rango 3,9-60); 31 tenían intestino corto, 8 dismotilidad, 5 diarrea intratable y 2 misceláneos. Veintiséis se intentaronadaptar inicialmente, 20 se incluyeron directamente como candidatos. La modalidad de trasplante se modificó durante su espera en 18. Todos recibieron tacrolimus y corticoides requiriendo 5 conversión a sirolimus posteriormente. Seis fallecieron el primer mes por sepsis/fallo multiorgánico (mala situación basal); 13 fallecieron tardíamente; observamos rechazo agudo en 20, rechazo crónico en 3, síndrome linfoproliferativo en 8 (fallecieron 6), y EICH en 5 (fallecieron 3). La supervivencia tras 5 años es del 65,2 % (51,7% el injerto). Desde 2006-2008,la supervivencia a los 6m, 1 y 3 años del paciente/injerto es 88,7/84,1,81,2/81,2 y 81,2/71,1%, respectivamente. Tras un seguimiento medio de 39 ± 29 meses, todos los pacientes vivos (n=27, 59%) son autónomos digestivos (70% ya sin estoma), están escolarizados, con mínimosingresos y buena calidad de vida. Conclusiones. El TI se afianza como alternativa de tratamiento en (..) (AU)

Objective. To analyze the evolution of Small Bowel Transplantation program since the beginning of the program. Matherial and methods. All children who underwent intestinal transplantation between 1997 and 2009 were retrospectively reviewed: epidemiological data, status before transplant, surgical technique, immunosupression, results, survival and long. term quality of life were analysed. Results. Fifty-two intestinal transplants were performed in 46 children (20 isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median age was 32m (range 7m-19a); weight 12,3 kg (range3,9-60); 31 had short gut syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous. Intestinal adaptation was initially attempted in 26 patients, without success, 20 were directly listed for transplant. The modality of transplant was modified in 17 while listed. Baseline immune supression consisted of tacrolimus and steroids, although 5 required conversion to Sirolimus later. Six died during the first month, due to sepsis/multiorganic failure (poor status at transplant);13 died during the long-term follow-up. Acute rejection was seen in 20,chronic rejection in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3died). Overall survival after 5 years of follow-up is 65,2 % (51,7% for (..) (AU)

[Need of hepatic bipartition or split in the transplant in children]. / Necesidad de la bipartición hepática o split en el trasplante en niños.

AIM: To analyze the benefits of Split (for adult and for child) in liver transplantation. PATIENT/METHODS: 1) Analysis of the waiting list mortality estimated on 228 inclusions for transplant since January 2004 to December 2008.2) Impact of the variant techniques (living-related donor and split) on the waiting list mortality in our patients. 3) Analysis of the outcome of 33 split livers which allowed to perform 66 transplants (1994-2008). RESULTS: Estimated as number of patients by 1,000 candidates by year of exposure, the waiting list mortality was 110 in children older than 5 year old, 180 in children from 2 to 5 year-old, 90 in children between 1 and 2 year-old and 510 in younger than 1 year (p<0.05 for the last group). 36/66 split grafts were implanted by our group. Five grafts were lost, 3 due to retransplantation and 2 due to death. Overall patient/graft survival alter 10 years of follow-up was 94.5% and 85.1%, respectively. The rest of the grafts (n=30), were used in other hospitals, and 4 were lost in the early postoperative period. Since the beginning of the study, 85.4% of children between 1 and 2 years, received a living-donor or a split graft, as only 59.9% in the younger than 1 year-old group. CONCLUSION: Our results absolutely justify the ethics of split liver transplantation for an adult and a child. Despite other factors, the benefits of the variant techniques in the 1-2 year-old group are obvious. Up to 60% optimization with these techniques in children younger than 1 year would not be yet enough in order to decrease the mortality waiting list down to that of the rest of the groups.

[Intestinal transplant: in what phase are we?]. / Trasplante intestinal: ¿en qué fase estamos?

OBJECTIVE: To analyze the evolution of Small Bowel Transplantation program since the beginning of the program. MATERIAL AND METHODS: [corrected] All children who underwent intestinal transplantation between 1997 and 2009 were retrospectively reviewed: epidemiological data, status before transplant, surgical technique, immunosupression, results, survival and long.term quality of life were analysed. RESULTS: Fifty-two intestinal transplants were performed in 46 children (20 isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median age was 32m (range 7m-19a); weight 12,3 kg (range 3,9-60); 31 had short gut syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous. Intestinal adaptation was initially attempted in 26 patients, without success, 20 were directly listed for transplant. The modality of transplant was modified in 17 while listed. Baseline immunosupression consisted of tacrolimus and steroids, although 5 required conversion to Sirolimus later. Six died during the first month, due to sepsis/multiorganic failure (poor status at transplant); 13 died during the long-term follow-up. Acute rejection was seen in 20, chronic rejection in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3 died). Overall survival after 5 years of follow-up is 65,2 % (51,7% for the graft). From 2006 to 2008, overall patient/graft survival at 6 m, 1 and 3 years after transplant is 88,7/84,1, 81,2/81,2 and 81,2/71,1%, respectively. After a median follw-up of 39 +/- 29 months, 27 patients are alive (59%), off TPN, (70% had their ostomy taken down), go to school, are scarcely hospitalized and enjoy a good quality of life. CONCLUSIONS: Intestinal transplantation has consolided itself as a good choice for irreversible intestinal failure, being feasible to achieve a normal life. Although overall survival diminishes over time, the center experience has improved the results. These patients need a very close follow-up, once transplant is over, in order to get an early diagnose of immunological complications.

Surgery of liver tumors in children in the last 15 years.

AIM: Aim of the study was to review our experience in the management of liver tumors in children over the last 15 years. PATIENTS AND METHODS: A cohort of 78 children with liver tumors managed in our institution between 1991 and 2006 was retrospectively reviewed. There were 45 males and 33 females with a mean age of 32 +/- 41 months at diagnosis. Most tumors were malignant (n = 57); the most frequently occurring tumor was hepatoblastoma (n = 47), followed by hepatocarcinoma (n = 5), sarcoma (n = 4), and lymphoma (n = 1). Vascular tumors (n = 12) predominated among the benign tumors followed by mesenchymal hamartoma (n = 4), focal nodular hyperplasia (n = 3), adenoma (n = 1), and inflammatory pseudotumor (n = 1). We reviewed the epidemiologic features, clinical presentation, diagnosis, treatment and outcomes. We employed MRI and angio-CT for SIOPEL PRETEXT staging and selected the management accordingly for malignant tumors. We analyzed the long-term survival using Kaplan-Meier curves. RESULTS: Benign tumors had an excellent outcome with both medical or surgical management. Of the malignant tumors 4 were PRETEXT I and were treated by left lateral segmentectomy with 100 % survival; 20 were PRETEXT II (12 left and 8 right lobe) and were treated by lobectomy of the corresponding side, except for 1 case which required OLT (90 % survival); 9 children had PRETEXT III tumors requiring trisegmentectomy or extended lobectomies with OLT in 1 case (77.7 % survival). Fourteen children had PRETEXT IV tumors: 10 received OLT and 9 of them are still alive (64.2 % survival). Overall survival was 80.8 %, and actuarial survival at 6 years was 82.2 %. Other malignant tumors had variable results. CONCLUSIONS: Outcomes have improved much in the last years. Surgical removal is necessary in most cases. Transplantation is a very useful adjunct. Treatment of these tumors should be concentrated in centers with expertise.

[Orthotopic liver transplantation in children younger than one year]. / Trasplante hepático en menores de un año.

BACKGROUND: Orthotopic liver transplantation (OLT) in children younger than one year is associated to higher waiting list mortality and alternative graft sources are required. We present our experience with this particular group of age. METHODS: Infants younger than one year who received an OLT between 1986 and 2005 were reviewed focused on graft and children survival depending on period and type of graft. Periods were 1:1986-1995; 2:1996-2000 and 3:2001-2005. We also evaluate cold ischemia time (CIT), graft lost causes and differences between CIT and anhepatic time (AT) depending on graft type. RESULTS: Eighty-three children received 103 OLT. Liver transplant indications were 59 (72%) biliary atresia, 8 (10%) metabolic causes, 6 (8%) liver failure, 3 (4%) cirrhosis and 7 (6%) miscelaneous. Patient and graft survival after 5 years was increased depending on period: 45% and 65% on period 1, 70% and 80% on period 2, 94% y 97% on period 3 (p < 0.0198). Thirty-seven grafts were reduced lobes (42%); 8 (21%), 17 (45%) and 12 (35%) during periods 1, 2 and 3 respectively and their 5 years survival rate was 68%. Twenty-four were whole grafts (31%); 11 (45%), 10 (45%) and 3 (14%) during periods 1, 2 and 3 and their 5 years survival rate was 63%. Fourteen grafts were living-related donor (16%); 1 (7%), 2 (14%) and 11 (79%) during periods 1, 2 and 3 and their 5 years survival rate was 93%. Eight (11%) were split; 0, 1 (12%) and 7 (90%) during periods 1, 2 and 3 and their 5 years survival rate was 100%. Average CIT depending on graft was: living donor 5,5 hours (IQR: 4-7), split 6,1 hours (IQR: 5-8), whole 9.2 hours (IQR: 6-11) and reduced 8.5 hours (IQR: 6-11) (p < 0.05). Average AT depending on graft was: living donor 1 hour (IQR: 0.5-1.5), split 1 hour (IQR: 0.5-1.4), whole 1,1 hours (IQR: 0.5-1.5) (p > 0.1). Twenty-four grafts were lost (28%): 10 (41%) were surgical related causes and 6/10 (60%) of them were whole grafts. CONCLUSIONS: Survival rates in children younger than one year are similar to another groups of age. There was a significant increase on graft survival according to transplantation group experience. A higher rate of graft lost is associated to whole grafts. Most frequent reasons of graft lose were related to sepsis and immunosuppresion. A significant shortening of CIT is observed in related living donor and split grafts.

Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

[Multidisciplinary approach in the management of intestinal failure]. / Tratamiento multidisciplinario del fallo intestinal.

OBJECTIVE: [corrected] Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients.

Trasplante hepático en menores de un año / Orthotopic liver transplantation in children younger than one year

Introducción. El trasplante hepático (TH) en menores de 1 año es técnicamente difícil, se asocia a mayor mortalidad en lista de espera y necesita técnicas alternativas por la escasez de órganos. Presentamos nuestra experiencia con el TH en este grupo de edad. Material y métodos. Revisamos en las historias de los menores de un año que recibieron un TH entre 1986 y 2005 indicaciones de TH, supervivencia del niño y el injerto según tipo de injerto y etapa (1:1986-1995; 2:1996-2000 y 3:2001-2005), causas de pérdida de injerto y diferencia de tiempo de isquemia fría (TIF) y tiempo de fase anhepática según tipo de injerto. Resultados. Ochenta y tres niños recibieron 103 TH; 59(72%) por atresia de vías biliares, 8(10%) por causas metabólicas, 6(8%) por fallo hepático, 3(4%) por cirrosis y 7(6%) por otras causas. La supervivencia a los 5 años del injerto y del niño aumento significativamente según etapa: 45% y 65% en la etapa 1, 70% y 80% en la etapa 2, 94% y 97% en la etapa 3 (p 0,1). Se perdieron 24 (28%) injertos: 10 (41%) por causas relacionadas con la cirugía y 6/10(60%) en higados enteros. Catorce injertos (58%) se perdieron por razones no relacionadas con la cirugía en forma de rechazo o sepsis. La tasa de retrasplante fue 9/20 (45%) con 1´6 injertos por niño, 7/30 (23%) con 1,2 injertos por niño, 2/33 (6%) con 1´06 injertos por niño en las etapas 1,2 y 3. Conclusiones. El TH en menores de 1 año obtiene resultados iguales o mejores que en otros grupos de edad. Existe un aumento de la supervivencia del injerto y del paciente así como una menor tasa de retrasplante con la experiencia del grupo. Hay más pérdidas del injerto relacionadas con la cirugía en hígados enteros. Las razones mas frecuentes de pérdidas del injerto estuvieron relacionadas con sepsis e inmunosupresión. El TIF es significativamente menor en injertos de donante vivo y Split (AU)

Background. Orthotopic liver transplantation (OLT) in children younger than one year is associated to higher waiting list mortality and alternative graft sources are required. We present our experience with this particular group of age. Methods. Infants younger than one year who received an OLT between 1986 and 2005 were reviewed focused on graft and children survival depending on period and type of graft. Periods were 1:1986-1995; 2:1996- 2000 and 3:2001-2005. We also evaluate cold ischemia time (CIT), graft lost causes and differences between CIT and anhepatic time (AT) depending on graft type. Results. Eighty-three children received 103 OLT. Liver transplant indications were 59 (72%) biliary atresia, 8 (10%) metabolic causes, 6 (8%) liver failure, 3 (4%) cirrhosis and 7 (6%) miscelaneous. Patient and graft survival after 5 years was increased depending on period: 45% and 65% on period 1, 70% and 80% on period 2, 94% y 97% on period 3 (p 0,1). Twenty-four grafts were lost (28%): 10(41%) were surgical related causes and 6/10 (60%) of them were whole grafts. Conclusions. Survival rates in children younger than one year are similar to another groups of age. There was a significant increase on graft survival according to transplantation group experience. A higher rate of graft lost is associated to whole grafts. Most frequent reasons of graft lose were related to sepsis and immunosuppresion. A significant shortening of CIT is observed in related living donor and split grafts (AU)

Tratamiento multidisciplinario del fallo intestinal / Multidisciplinary approach in the management of intestinal failure

Introducción. Aunque se han producido importantes avances en el terreno del fallo intestinal (FI), su tratamiento es a menudo aplicado por grupos compartimentados, con escasa interrelación, y ello influye negativamente sobre los resultados. Objetivo. Analizar los resultados en el tratamiento del FI en el niño a cargo de un programa multidisciplinar de Rehabilitación Intestinal que integra los tres procedimientos básicos: 1) técnicas de soporte nutricional; 2) farmacoterapia; 3) cirugía (que incluye reconstrucción autóloga del intestino y trasplante intestinal (TI). Material y métodos. 71 casos de FI prolongado (40 niñas, 31 niños), entre Julio 1997 y Abril 2006. Sólo se incluyen casos de FI considerados candidatos potenciales a TI. Resultados. Las causas de FI fueron síndrome de intestino corto 52; trastornos de motilidad 16; diarreas intratables 3. En 56 casos el FI era de comienzo neonatal, asociado a prematuridad en 18. El 76% de los niños (n=54) fueron enviados desde otros centros. Se obtuvo adaptación intestinal en 14 niños, en 7 tras reconstrucción autóloga (asociada en uno a hormona de crecimiento –HC-), y optimización de la dieta en 5 (uno asociada a HC); otro niño referido para TI por pseudoobstrucción y pérdida de accesos venosos adaptó tras comprobar que padecía una enfermedad de Hirschsprung. Cuatro niños fallecieron antes de poder ser incluidos para TI; otros 3 presentaban comorbilidades que contraindicaron el TI; 9 permanecen estables con nutrición parenteral domiciliaria, y 43 fueron puestos en lista (incluye dos niños que adaptaron tras ser incluidos y salieron de la lista). De ellos, 8 fallecieron en lista (todos candidatos a trasplante combinado incluyendo hígado), y 25 recibieron un total de 29 injertos (16 de hígado-intestino, 9 de intestino aislado, 3 multiviscerales y 1 hepático). Dieciséis de los niños trasplantados (64%) están vivos, de los cuales 14 están libres de NP (incluyendo los 4 niños retrasplantados), y dos están anentéricos en espera de retrasplante. La mortalidad en los niños trasplantados se relacionó principalmente con el mal estado previo al TI. Dos niños fallecieron por linfoma. Conclusiones. La integración de todas las modalidades de tratamiento del FI por un grupo multidisciplinar de profesionales con interés en el FI optimiza los resultados, gracias a la concentración de la experiencia, la posibilidad de interacción entre las distintas modalidades de tratamiento y la agilidad para poder realizar cambios rápidos de indicación. La posibilidad de realizar trabajos clínicos experimentales útiles se ve igualmente favorecida por la implementación de centros de Rehabilitación Intestinal (AU)

OBJETIVE: Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients (AU)

Comparative study between living and cadaveric donors in pediatric liver transplantation.

UNLABELLED: We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). MATERIAL AND METHODS: The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment (n = 22), left lobe (n = 3), and right lobe (n = 2). In the CDLT group, the grafts were split in situ (n = 10), hepatic reduction (n = 9) and whole liver (n = 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes >2000 U/L), surgical complications, rejection, and resource consumption. RESULTS: Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT (P = NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (P = NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P = .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT (P < .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. CONCLUSIONS: The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.

Intestinal transplantation in children: differences between isolated intestinal and composite grafts.

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.

[Results of an intestinal transplantation program in Spain. Five years later]. / Resultados de un programa de trasplante intestinal. Cinco años después.

BACKGROUND: More than two thirds of all intestinal transplantations (ITx) performed around the world correspondent to recipients younger than 18. OBJECTIVE: To analyze our 5-year experience in pediatric ITx. PATIENTS: We assessed the outcome of the 19 children included in list out of 41 patients considered for ITx from 1997. The main cause of intestinal failure was short bowel syndrome (14) followed by intestinal motility disorders (3) and congenit disorders of intestinal epithelium (CDIE) (2). The median of age, at the moment of including in the list, was 0.9 years (range 0.4-17) and median of weight was 6.4kg (range 0.4-29.3). Ten children were included for liver and small bowel transplantation (LSBTx), 7 to isolated small bowel (SBTx), and 2 for multivisceral transplantation (MVTx). Indications for SBx were hepatic fibrosis/cirrhosis (10), hepatic fibrosis in evolution (5) (to avoid later LSBTx), intractable diarrhoea (1), recurrent line infections (1), lost of central vein access (1), and bad quality of life in one. RESULTS: Five children died in the waiting list, after a median time of 325 days (range 19-581). Seven remain in the waiting list (median 139 days, range 30-778). In 3 of these the indication changed from SBTx to LSBTx because of progression to end stage liver disease. Six children recieved seven grafts (1 MVTx, 4 LSBTx, 2 SBx) after a median time in the waiting list of 352 days (range 66-732). Six out of seven grafts achieved normal function and all survivals reached full digestive autonomy after Tx. We had to rejection episodes, one with good response to medical treatment and one that required removal of intestinal allograft and later LSBTx. Two children died 1 because of problem not related to the procedure (hemorrage following liver biopsy) and one girl died 29 months after transplant due to post-transplantation lymphoproliferative disease. CONCLUSIONS: ITx is a realistic alternative in our country for children with intestinal failure. The main problems are immunologic (rejection, lynphoproliferative and disease) Shortage of small weight donors is a dramatic limitation that prompts the discussion of surgical alternatives.

[The multifocal hepatic hemangioendothelioma. Is always a benign tumor?]. / Hemangioendotelioma multifocal hepático infantil. Es siempre un tumor benigno?

UNLABELLED: The hepatic multicentric haemangioma is defined by its extension, affecting all the mass of the liver. The high mortality associated with it is mostly related with the complications produced by its enormous size (haemodynamic, platelet trapping, spontaneous rupture and bleeding). There is a general belief that is a benign tumor with possibility of spontaneous regression and cure. AIM: Retrospective analysis of our recent cases of MHH with the purpose of: 1 degrees) To show the evolution and results. 2 degrees) To realize if the "benign character" of the tumor is real or if some cases may be considered as malignant tumors. MATERIAL AND METHODS: 10 cases of MHH treated in the last 10 years. In 9 the age of presentation was less than 6 months and one patient was diagnosed at 3 and half years. The diagnosis was confirmed by image techniques in 7 cases and by biopsy in 3. In 7 patients extrahepatic vascular lesions were associated prior to the treatment. Methylprednisolone was given to all the cases and alpha-2-interferon was administered to the patients that not responded to the steroids. Vincristine was added to 2 patients. In two cases the hepatic artery embolization was tried and one patient had a liver transplant. RESULTS: Four children had at least one episode of congestive cardiac insufficiency, two patients suffered a consumption coagulopathy (Kasabach Merrit syndrome), and one presented acute hepatic failure. In six children it has been complete regression of the tumor, one more is still under treatment and three died. The dead were produced by the malignant behavior of the tumor in one case (tumoral rupture of a MHH recurrence in the transplanted liver), and possibly in other (intracranial haemorrhage and hepatic failure in a liver transplantation candidate without demonstrated extrahepatic extension in the previous studies, but with multiorgan dissemination at autopsy. In both cases it was impossible to discover signs of histologic or biologic malignancy neither in the primitive lesion nor in the metastasis. CONCLUSIONS: 1a) The regression of the MHH, spontaneous or induced by the treatment is frequent. 2a) Some cases of MHH are aggressive and develop local recurrences and distant metastasis. 3a) The discrimination between MHH of "benign" or "malignant" behaviour is not possible. 4a) Despite of the unpredictable biological conduct of the tumor, the liver transplantation must be considered as an option in the symptomatic cases that not respond to the conventional treatment.

[Prognostic factors in pediatric liver transplantation. Multivariate analysis]. / Factores pronósticos del trasplante hepático pediátrico. Análisis multivariante.

AIM: To analyze independent risk factors associated with poor graft and patient survival in a series of 292 pediatric liver transplants (PLT) performed in 234 children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and patient survival analysis in 45 variables related to pretransplant patient status, surgical technique and donor conditions. 2. Variables found with univariate analysis to be associated with outcome were entered into a stepwise backward proportional hazard model (Cox), to determine independent prediction of outcome. RESULTS: 11 variables influence the graft survival: recipient age, z-score recipient height, UNOS status, recipient and donor weight, transplant for immune hepatitis, platelet transfusion during the transplant, blood index > 4 during the surgery, type of arterial reconstruction, retransplantation and era of the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000). Four of those variables are independent in the multivariate analysis: UNOS 1 status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient < 3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and era (OR of first and second versus third era respectively 3.93 and 2.81). The independent variables influencing the patient survival were: children receiving more than one graft children less than 3 years old and transplant era. CONCLUSIONS: Liver transplant in small children is associated with an increased risk of graft loss and patient dead. The experience of the hospital in pediatric liver transplantation improves the results, particularly in small children.

[Activity of a pediatric intestinal transplantation program in Spain]. / Actividad de un programa de trasplante intestinal pediátrico en España.

AIM: To analyze the outcome of children with intestinal failure (IF) included as candidates for intestinal transplantation (IT). Patients, Eight out of 23 children with IF assessed since July 1997 met criteria for IT and were included on the waiting list. The causes of IT were Short Bowel Syndrome (SBS) in 6 and Microvillus Inclusion Disease (MID) in 2. The indication of IT were end stage liver disease (ESLD) in 5 (related to total parenteral nutrition administration, TPN), progressive hepatic fibrosis in 2 and loss of venous access in 1. The patients with ESLD were included for combined liver-small bowel transplantation (LSBT) and the remaining for isolated intestinal transplantation (IIT). RESULTS: Two children died waiting for LSBT, 4 patients are on the waiting list, 2 for LSBT and 2 for IIT (length of stay: 4-11 months). Two children were transplanted, one with IIT in a 2.5 years old boy with MID, and one with LSBT in a 22 months girl with SBS and ESLD. Both patients recovered intestinal function after transplantation and are a live (follow-up of 19 and 10 months respectively). The LSBT's patient is under treatment for postransplant lymphoproliferative disease (PTLD). CONCLUSIONS: The lack of suitable donors for the small children candidate to IT explains the long period of stay on the waiting list and the high pretransplant mortality. Two strategies are possible; early referral of children with IF to a transplant center and surgical techniques like ex vivi-hepatic reductions of the LSB graft.