Extensive Hepatectomy as an Alternative to Liver Transplant in Advanced Hepatoblastoma: A New Protocol Used in a Pediatric Liver Transplantation Center.

BACKGROUND: Surgery is a key factor in the treatment of hepatoblastoma, but choosing between an aggressive resection and liver transplant may be an extremely difficult task. The aim of this study was to describe the outcomes of patients with advanced hepatoblastoma: pretreatment extent of disease (PRETEXT)/post-treatment extent of disease (POST-TEXT) III and IV undergoing aggressive resections or living donor liver transplant in cases involving the entire liver. Based on this experience, a new protocol for the treatment of these patients was proposed. METHODS: A retrospective study included patients with advanced hepatoblastoma (POST-TEXT III and IV) who were referred for a liver transplant from 2010 to 2017. RESULTS: A total of 24 children were included: 13 (54.2%) were male, with a median age at diagnosis of 42 months (range, 15-120 months), and a history of prematurity was identified in 20.8% of the patients. Ten cases (41.7%) were staged as PRETEXT/POST-TEXT III, and 12 cases (50.0%) were staged as PRETEXT/POST-TEXT IV. Two patients were referred after posthepatectomy recurrence. Five patients underwent a liver transplant, with recurrence and death in 2 patients (40.0%) within a mean period of 6 months. In the extensive hepatectomy group, there was recurrence in 6 patients (31.6%), with disease-free outcomes and overall survival in 63.2% and 94.7% of patients, respectively. CONCLUSION: In cases of advanced hepatoblastoma, an extensive surgical approach is a valuable option. The fact that the team was fully prepared to proceed with living donor liver transplant allowed the surgeon to be more aggressive and to switch to transplantation when resection was not possible.

Remote Ischemic Preconditioning Is Efficient in Reducing Hepatic Ischemia-Reperfusion Injury in a Growing Rat Model and Does Not Promote Histologic Lesions in Distant Organs.

OBJECTIVE: Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. METHODS: Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. RESULTS: The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. CONCLUSION: In young animals, the beneficial effects of RIP are more evident than those of DIP.

Comparison of the Results of Living Donor Liver Transplantation Due to Acute Liver Failure and Biliary Atresia in a Quaternary Center.

OBJECTIVE: The objective of this study was to compare the complications, outcomes, and survival prevalence in patients undergoing living donor liver transplantation due to biliary atresia (BA) or acute liver failure (ALF). RESULTS: In the period of June 1998-July 2016, 199 children underwent living transplantation due to BA or ALF. Of these 199, 184 were included in the analysis. The average age, weight, and body mass index of BA patients were lower than those of ALF (P < .001). The chi-square test showed a higher prevalence of infection in transplant recipients due to BA (P = .0001) and a higher prevalence of hepatic artery stenosis in those who underwent transplantation due to ALF (P = .001). In the multivariate analysis, the infection remains statistically more prevalent in the BA group (95% confidence interval [CI], 0.20-0.60), while hepatic artery stenosis loses significance. The mortality rate was similar in both groups and the survival in 5 years also. The prevalence of hepatic artery thrombosis, portal vein thrombosis/stenosis, biliary stenosis, and acute and chronic cellular rejection showed no statistical difference between the two groups. CONCLUSION: Living donor liver transplantation should be a valid option in cases of fulminant hepatitis with an indication for liver transplantation, especially in places where the number of cadaverous donors is low and the length of time on the waiting list is high.

Liver regeneration model in growing rats with hepatic artery ligation: histologic and molecular studies.

BACKGROUND: Liver transplantation is an effective treatment for irreversible liver diseases. The incidence of hepatic artery thrombosis remains high. Our objective was to analyze the effect of ligature of the hepatic artery on liver regeneration in a growing animal model. METHODS: Seventy-five male Wistar rats were divided into the following 3 groups: group 1 (sham, G1): incision without intervention; group 2 (G2): 70% hepatectomy; group 3 (G3): 70% hepatectomy and ligation of the hepatic artery. Preceding the 70% hepatectomy, a hepatic artery ligature was performed with resection of a segment of the artery. The liver specimens were stained with hematoxylin-eosin, and immunohistochemical staining for Ki-67 was performed. The expression of the interleukin (IL) 6 gene was studied by means of reverse-transcription polymerase chain reaction. RESULTS: G2 and G3 demonstrated similar tendencies toward an increase in the gain weight ratio over time. The mitotic activity was significantly lower at 72 hours in G3 than in G2. There was no difference between Ki-67 staining between G2 and G3. The expression of the IL-6 gene was present in all of the groups, lower in G1, with no difference between G2 and G3. CONCLUSIONS: The experimental model was feasible and adequate for these investigations. Hepatectomy stimulated hepatocyte proliferation, and the obstruction of the arterial flow did not affect liver regeneration.

Longitudinal assessment of lung area measurements by two-dimensional ultrasound in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate lung growth in healthy fetuses and those with congenital diaphragmatic hernia (CDH) using two-dimensional (2D) ultrasound. METHODS: Fetal right lung measurements obtained by 2D ultrasound between 19 and 37 weeks' gestation were evaluated longitudinally in 66 healthy fetuses and 52 fetuses with isolated left-sided CDH. Right lung areas were determined by the 'tracing' and 'longest-diameters' methods and, subsequently, lung area-to-head circumference ratios (LHRs) were calculated. Functions fitted to these size parameters with respect to gestational age were evaluated for three sets of group-wise comparisons: (1) healthy vs CDH fetuses; (2) different degrees of severity of CDH; and (3) CDH fetuses that survived vs those that died by 6 months postpartum. RESULTS: There was a significantly slower increase in right lung areas and LHRs with advancing gestational age in CDH fetuses than in healthy individuals (P < 0.05). Compared to those with milder forms of CDH, lung areas and LHRs of fetuses with more severe forms displayed a smaller increase (P < 0.05) and LHRs of fetuses with severe CDH did not increase during pregnancy (P > 0.05). Individuals who died postpartum did not show any increase in LHR (P > 0.05) throughout gestation. CONCLUSIONS: The right lung area and LHR, calculated using either the longest-diameters or tracing method, display reduced growth rates during gestation in cases of isolated left-sided CDH as compared with healthy fetuses. The growth curve characteristics of fetal lung areas and LHRs may be useful for predicting neonatal mortality.

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

Dynamic expression of desmin, α-SMA and TGF-ß1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats.

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-ß1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT-PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-ß1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT-PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-ß1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT-PCR technique was more sensitive to expression changes than the semiquantitative method.

Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: preliminary results.

OBJECTIVE: To evaluate the effect of early fetoscopic tracheal occlusion (FETO) (22-24 weeks' gestation) on pulmonary response and neonatal survival in cases of extremely severe isolated congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter study involving fetuses with extremely severe CDH (lung-to-head ratio < 0.70, liver herniation into the thoracic cavity and no other detectable anomalies). Between August 2010 and December 2011, eight fetuses underwent early FETO. Data were compared with nine fetuses that underwent standard FETO and 10 without fetoscopic procedure from January 2006 to July 2010. FETO was performed under maternal epidural anesthesia, supplemented with fetal intramuscular anesthesia. Fetal lung size and vascularity were evaluated by ultrasound before and every 2 weeks after FETO. Postnatal therapy was equivalent for both treated fetuses and controls. Primary outcome was infant survival to 180 days and secondary outcome was fetal pulmonary response. RESULTS: Maternal and fetal demographic characteristics and obstetric complications were similar in the three groups (P > 0.05). Infant survival rate was significantly higher in the early FETO group (62.5%) compared with the standard group (11.1%) and with controls (0%) (P < 0.01). Early FETO resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with standard FETO (P < 0.01). CONCLUSIONS: Early FETO may improve infant survival by further increases of lung size and pulmonary vascularity in cases with extremely severe pulmonary hypoplasia in isolated CDH. This study supports formal testing of the hypothesis with a randomized controlled trial.

Mechanical bowel preparation for esophagocoloplasty in children: is it really necessary?

Esophagocoloplasty is a commonly performed procedure for esophageal replacement in children. Traditionally, mechanical bowel preparation (MBP) is performed before this operation. However, this practice has been questioned, initially in adults and now in children. The aim of this study was to evaluate the influence of MBP on esophagocoloplasty in a series of children. Data collected from 164 patients who underwent esophagocoloplasty in the Pediatric Surgery Division, University of São Paulo Medical School, from February 1978 to July 2011 were reviewed for postoperative complications. In 134 patients, at least one kind of MBP was performed before the surgery (PREP group). MBP was omitted in 30 patients (NO-PREP group). There was no statistical difference between the groups in the rates of evisceration, colocolic, or cologastric anastomotic dehiscence and death. However, in the NO-PREP group, the incidence of cervical leakage (6.6%) was significantly decreased in comparison with the classical PREP group (25.3%) (P= 0.03). The results of this study suggest that the omission of MBP has a positive impact on the incidence of postoperative complications in esophagocoloplasty.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.

OBJECTIVE: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. METHODS: Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. RESULTS: Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). CONCLUSION: FETO improves neonatal survival in cases with isolated severe CDH.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters.

OBJECTIVES: To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). METHODS: Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). RESULTS: Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e-LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). CONCLUSIONS: Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis.

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.

Hepatic artery graft in pediatric liver transplantation: single-center experience with 58 cases.

INTRODUCTION: The use of arterial grafts (AG) in pediatric orthotopic liver transplantation (OLT) is an alternative in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, and retransplantations (re-OLT) due to hepatic artery thrombosis (HAT). AG have been crucial to the success of the procedure among younger children. Herein we have reported our experience with AG. METHODS: We retrospectively reviewed data from June 1989 to June 2010 among OLT in which we used AG, analyzing indications, short-term complications, and long-term outcomes. RESULTS: Among 437 pediatric OLT, 58 children required an AG. A common iliac artery interposition graft was used in 57 cases and a donor carotid artery in 1 case. In 38 children the graft was used primarily, including 94% (36/38) in which it was due to poor hepatic arterial inflow. Ductopenia syndromes (n = 14), biliary atresia (BA; n = 11), and fulminant hepatitis (n = 8) were the main preoperative diagnoses among these children. Their mean weight was 18.4 kg and mean age was 68 months. At the mean follow-up of 27 months, multiple-organ failure and primary graft nonfunction (PNF) were the short-term causes of death in 9 children (26.5%). Among the remaining 29 patients, 2 (6,8%) developed early graft thrombosis requiring re-OLT; 5 (17%) developed biliary complications, and 1 (3.4%) had asymptomatic arterial stenosis. In 20 children, a graft was used during retransplantation. The main indication was HAT (75%). BA (n = 15), ductopenia syndromes (n = 2), and primary sclerosing cholangitis (n = 2) were the main diagnoses. Their mean weight was 16.7 kg and age was 65 months. At a mean follow-up of 53 months, 7 children died due to multiple-organ failure or PNF. Among the remaining 13 patients, 3 developed biliary complications and 1 had arterial stenosis. No thrombosis was observed. CONCLUSION: The data suggested that use of an AG is useful alternative in pediatric OLT. The technique is safe with a low risk of thrombosis.

Orthotopic liver transplantation in biliary atresia: a single-center experience.

INTRODUCTION: Biliary atresia (BA) is the leading indication for orthotopic liver transplantation (OLT) among children. However, there are technical difficulties, including the limited dimensions of anatomical structures, hypoplasia and/or thrombosis of the portal vein and previous portoenterostomy procedures. OBJECTIVE: The objective of this study was to present our experience of 239 children with BA who underwent OLT between September 1989 and June 2010 compared with OLT performed for other causes. METHODS: We performed a retrospective analysis of patient charts and analysis of complications and survival. RESULTS: BA was the most common indication for OLT (207/409; 50.6%). The median age of subjects was 26 months (range, 7-192). Their median weight was 11 kg (range, 5-63) with 110 children (53.1%) weighing ≤10 kg. We performed 126 transplantations from cadaveric donors (60.8%) and 81 from living-related donors (LRD) (39.2%). Retransplantation was required for 31 recipients (14.9%), primarily due to hepatic artery thrombosis (HAT; 64.5%). Other complications included the following: portal vein thrombosis (PVT; 13.0%), biliary stenosis and/or fistula (22.2%), bowel perforation (7.0%), and posttransplantation lymphoproliferative disorder (PTLD; 5.3%). Among the cases of OLT for other causes, the median age of recipients was 81 months (range, 11-17 years), which was higher than that for children with BA. Retransplantation was required in 3.5% of these patients (P < .05), mostly due to HAT. The incidences of PVT, bowel perforation, and PTLD were significantly lower (P < .05). There was no significant difference between biliary complications in the 2 groups. The overall survival rates at 1 versus 5 years were 79.7% versus 68.1% for BA, and 81.2% versus 75.7% for other causes, respectively. CONCLUSIONS: Children who undergo OLT for BA are younger than those engrafted for other causes, displaying a higher risk of complications and retransplantations.

Rex shunt for acute portal vein thrombosis after pediatric liver transplantation in children with biliary atresia.

BACKGROUND/PURPOSE: Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT. METHODS: Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day. RESULTS: The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date. CONCLUSIONS: The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.

Should patients with esophageal atresia be submitted to esophageal substitution before they start walking?

Esophagocoloplasty and gastric transposition are two major methods for esophageal substitution in children with esophageal atresia, and there is broad agreement that these operations should not be performed before the children start walking. However, there are some reported advantages of performing such operations in the first months of life or in the neonatal period. In this study, we compared our experience with esophageal substitution procedures performed in walking children with esophageal atresia, with the outcomes of children who had the operation before the third month of life reported in the literature. The purpose of this study was to establish if we have to wait until the children start walking before indicating the esophageal replacement procedure. From February 1978 to October 2009, 129 children with esophageal atresia underwent esophageal replacement in our hospital (99 colonic interpositions and 30 gastric transpositions). The records of these patients were reviewed for data regarding demographics, complications (leaks, graft failures, strictures, and graft torsion), and mortality and compared with those reported in the two main articles on esophageal replacement in the neonatal period or in patients less than 3 months of age. The main complication of our casuistic was cervical anastomosis leakage, which sealed spontaneously in all except in four patients. One patient of the esophagocoloplasty group developed graft necrosis and three patients in the gastric transposition group had gastric outlet obstruction, secondary to axial torsion of the stomach placed in the retrosternal space. The long-term outcome of the patients in both groups was considered good to excellent in terms of normal weight gain, absence of dysphagia, and other gastrointestinal symptoms. The comparisons of the main complications and mortality rates in walking children with esophageal substitutions performed in the first months of life showed that the incidences of cervical anastomotic leaks and graft failures were similar, but mortality rate in the first few months of life was significantly greater than that observed in our group of patients (P= 0.001). Based on the comparison of our results with those of published series, we conclude that the recommendation of performing esophagocoloplasty or total gastric transposition in children with esophageal atresia after they start walking is still valid.

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.