João Gilberto Maksoud-Filho

Hepatic venous reconstruction in pediatric living‐related donor liver transplantation – Experience of a single center

Abstract:  In pediatric patients submitted to living related liver transplantation, hepatic venous reconstruction is critical because of the diameter of the hepatic veins and the potential risk of twisting of the graft over the line of the anastomosis. The aim of the present study is to present our experience in hepatic venous reconstruction performed in pediatric living related donor liver transplantation. Fifty‐four consecutive transplants were performed and two methods were utilized for the reconstruction of the hepatic vein: direct anastomosis of the orifice of the donor left or left and middle hepatic veins and the common orifice of the recipient left and middle hepatic veins (group 1–26 cases), and wide triangular anastomosis after creating a wide triangular orifice in the recipient inferior vena cava at the confluence of all the hepatic veins with an additional longitudinal incision in the inferior angle of the orifice (group 2–28 cases). In group 1, eight patients were excluded because of graft problems in the early postoperative period and five among the remaining 18 patients (27.7%) presented stricture at the site of the hepatic vein anastomosis. All these patients had to be submitted to two or three sessions of balloon dilatations of the anastomoses and in four of them a metal stent had to be placed. The liver histopathological changes were completely reversed by the placement of the stent. Among the 28 patients of the group 2, none of them presented hepatic vein stenosis (p = 0.01). The results of the present series lead to the conclusion that hepatic venous reconstruction in pediatric living donor liver transplantation must be preferentially performed by using a wide triangulation on the recipient inferior vena cava, including the orifices of the three hepatic veins. In cases of stenosis, the endovascular dilatation is the treatment of choice followed by stent placement in cases of recurrence.

The outcome of newborns with abdominal wall defects according to the method of abdominal closure: the experience of a single center

Recent reports suggest that the technique of abdominal closure in neonates with anterior abdominal wall defects (AWD) correlates with the outcome. The aim of this study is to analyze factors related to mortality and morbidity, according to the technique of abdominal closure of these neonates. Retrospective analysis of charts from 76 consecutive neonates with AWD treated in a single institution. They were divided according to the type of abdominal wall closure: group I: primary closure, group II: silo followed by primary closure and group III: silo followed by polypropylene mesh. Outcome was analyzed separately for neonates with gastroschisis and omphalocele. There were 13 deaths (17.1%). Mortality for neonates with isolated defects was 9.6%. Mortality rate was similar in all groups for either neonates with gastroschisis or omphalocele. Postoperative complications were not significantly different among groups except for a prolonged time of hospitalization in group III. Mortality rate is not correlated with the type of abdominal closure. Neonates with primary closure or with other methods of abdominal wall closure had similar rate of postoperative complications. Neonates with mesh closure of the abdomen have prolonged hospitalization. The use of a polypropylene mesh is a good alternative for neonates whose primary closure or closure after silo placement is not possible.

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: experience of a single center.

Abstract:  Few studies have evaluated the long‐term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long‐term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI‐induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long‐term improvement in renal function parameters with no additional risks.

Living Related Donor Liver Transplantation in Children

OBJECTIVE The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors. METHODS We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010. RESULTS Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), α-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed ≤10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis). CONCLUSIONS Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.

Sirolimus in pediatric liver transplantation: a single-center experience.

BACKGROUND AND AIMS Liver transplantation (OLT) in children has seen significant improvements in recent years. Long-term immunosuppressive strategies have focused on avoiding the risks of long-term immunosuppression, particularly nephrotoxicity, de novo malignancy and late infections. Since its introduction in renal transplantation in 1999, sirolimus (SRL) has been used by an increasing number of liver transplant centers. The aim of this study was to review the experience using SRL in pediatric liver transplant recipients at a single center. METHODS Between 1989 and 2006, 318 children underwent OLT including 13 who were converted to SRL therapy because of tacrolimus-related side effects. The indications were posttransplant lymphoproliferative disease (PTLD; n = 11), nephrotoxicity (n = 1), and de novo autoimmune hepatitis (n = 1). One patient with PTLD previously concurrently displayed chronic rejection. SRL dosages ranged between 0.4 and 5 mg/d. The median duration of follow-up was 18 months. RESULTS PTLD recurred in 1 patient. There were no episodes of acute rejection. One child developed hyperlipidemia that resolved with diet and medication. CONCLUSIONS Conversion from tacrolimus to SRL in selected pediatric liver transplant recipients is safe. Children with PTLD may benefit from immunosuppression with SRL after liver transplantation.

Successful treatment of de novo autoimmune hepatitis and cirrhosis after pediatric liver transplantation.

Abstract: Over a 15‐yr period of observation, among the 205 children who underwent liver transplantations, one of them developed a particular type of late graft dysfunction with clinical and histological similarity to autoimmune hepatitis. The patient had α1‐antitrypsin deficiency and did not previously have autoimmune hepatitis or any other autoimmune disease before transplantation. Infectious and surgical complications were excluded. After repeated episodes of unexplained fluctuations of liver function tests and liver biopsies demonstrating reactive or a biliary pattern, without any corresponding alteration of percutaneous cholangiography, a liver‐biopsy sample taken 4 yr after the transplant showed active chronic hepatitis progressing to cirrhosis, portal lymphocyte aggregates, and a large number of plasma cells. At that time, autoantibodies (gastric parietal cell antibody, liver–kidney microsomal antibody, and anti‐hepatic cytosol) were positive and serum IgG levels were high. Based on these findings of autoimmune disease, a diagnosis of ‘de novo autoimmune hepatitis’ was made. The treatment consisted of reducing the dose of cyclosporine, reintroduction of corticosteroids, and addition of mycophenolate mofetil. After 19 months of treatment, a new liver‐biopsy sample showed marked reduction of portal and lobular inflammatory infiltrate, with regression of fibrosis and of the architectural disruption. At that time, serum autoantibodies became negative. The last liver‐biopsy sample showed inactive cirrhosis and disappearance of interface hepatitis and of plasma cell infiltrate. Presently, 9 yr after the transplantation, the patient is doing well, with normal liver function tests and no evidence of cirrhosis. Her immunosuppressive therapy consists of tacrolimus, mycophenolate mofetil, and prednisolone. In conclusion, the present case demonstrates that de novo autoimmune hepatitis can appear in liver‐transplant patients despite appropriate anti‐rejection immunosuppression, and triple therapy with tacrolimus, mycophenolate mofetil, and prednisolone could sustain the graft and prevent retransplantation.

Long-term follow-up of children with extrahepatic portal vein obstruction: impact of an endoscopic sclerotherapy program on bleeding episodes, hepatic function, hypersplenism, and mortality

BACKGROUND Endoscopic sclerotherapy (ES) has been the standard treatment for children with idiopathic extrahepatic portal vein obstruction (EHPVO). Portosystemic shunts are indicated when variceal bleeding cannot be controlled by ES. Recently, mesenteric left portal vein bypass was indicated as a surgical intervention and preventative measure for hepatic dysfunction in children with long-term EHPVO. Nevertheless, there is a lack of published data confirming the extent of hepatic dysfunction, hypersplenism, and physical development in children with long-term follow-up. METHOD We retrospectively verified the long-term outcomes in 82 children with EHPVO treated with ES protocol, focusing on mortality, control of bleeding, hypersplenism, and consequent hepatic dysfunction. RESULTS Of the children, 56% were free from bleeding after the initiation of ES. The most frequent cause of rebleeding was gastric varices (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four patients underwent surgery as a consequence of uncontrolled gastric varices. There were no deaths. Most patients showed good physical development. We observed a mild but statistically significant drop in factor V motion, as well as leukocyte and platelet count. CONCLUSION Endoscopic sclerotherapy is an efficient treatment for children with EHPVO. The incidence of rebleeding is low, and there was no mortality. Children develop mild liver dysfunction and hypersplenism with long-term follow-up. Only a few patients manifest symptoms of hypersplenism, portal biliopathy, or liver dysfunction before adolescence.

Multiple clinical presentations of lymphoproliferative disorders in pediatric liver transplant recipients: a single-center experience.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naïve prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

Posterior reversible encephalopathy syndrome after liver transplantation in children: a rare complication related to calcineurin inhibitor effects.

Santos MM, Tannuri ACA, Gibelli NE, Ayoub AA, Maksoud‐Filho JG, Andrade WC, Velhote MCP, Silva MM, Pinho ML, Miyatani HT, Suzuki L, Tannuri U. Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects.
Pediatr Transplantation 2011: 15:157–160.

The effects of prenatal intraamniotic surfactant or dexamethasone administration on lung development are comparable to changes induced by tracheal ligation in an animal model of congenital diaphragmatic hernia

BACKGROUND/PURPOSE Lung surfactant deficiency contributes to the pathophysiology of congenital diaphragmatic hernia (CDH) and the high neonatal mortality rate. Acceleration of lung surfactant system maturation by prenatal administration of hormones has been described in animal models of CDH. However, in utero tracheal ligation (TL) is the best method to accelerate lung growth and reverse the pulmonary hypoplasia associated with CDH. Although this method offers promise, its application in humans is limited. The aim of this study was to investigate a new noninvasive therapeutic strategy, that is, the prenatal intraamniotic administration of exogenous porcine surfactant or dexamethasone, and compare it with the effects of TL in an animal model of CDH. METHODS Twenty-four pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 to create CDH in 26 fetuses. Five groups of animals were studied: (1) Control, nonoperated fetuses (n=14), (2) CDH (n=6), (3) CDH plus TL (n 6), (4) CDH plus intraamniotic administration of Curosurf (40 mg; n=6), and (5) CDH plus intraamniotic infusion of dexamethasone (0.4 mg; n=8). On gestational day 30, the fetuses were delivered by cesarean section. Functional studies (lung hysteresis curves and lung distensibility), weight and volume of lungs, histopathologic and histomorphometric analysis of lungs were performed. RESULTS The authors demonstrated that the hysteresis curve of CDH animals was shifted downward in comparison with controls. The analyses of curves standardized for lung weight indicated that intraamniotic administration of surfactant or dexamethasone improved lung compliance in comparison with controls and CDH fetuses, but TL had no effect on this parameter. Lung distensibility (maximum lung volume at 32 cm of water pressure per gram of lung) was reduced by CDH, but this parameter was increased by intraamniotic administration of drugs and not by TL (P< .05). CDH decreased the weight and volume of lungs (P< .05), and these changes were reversed only by TL, which prevented the herniation of the liver from the abdomen to the thorax. Histologically, CDH lungs treated with TL or intraamniotic administration of drugs demonstrated structural patterns similar to those of controls. Histomorphometric studies proved that CDH promoted significant thickening of septa walls (P< .05), and all the therapeutic methods could reverse this alteration to control values. The alveolar number per area in control lungs, CDH, and CDH plus TL lungs were similar, but in CDH plus surfactant and CDH plus dexamethasone lungs, the decreased number per area (P< .05) demonstrated that the alveolar airspace was increased. CONCLUSION From these data the authors conclude that intraamniotic surfactant or dexamethasone administration is capable of preventing pulmonary hypoplasia in fetuses with CDH, and thus, this method may be a substitute for TL.