Current management of biliary atresia based on 35 years of experience at a single center.

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p<0.001), and jaundice was resolved in 15 patients (55.6% - p=0.021), with a survival rate of the native liver of 66.7%. CONCLUSION: Primary surgical exploration of the biliary tract without previous biopsy was effective at improving the prognostic indicators of patients with biliary atresia undergoing Kasai portoenterostomy.

Current management of biliary atresia based on 35 years of experience at a single center

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p<0.001), and jaundice was resolved in 15 patients (55.6% - p=0.021), with a survival rate of the native liver of 66.7%. CONCLUSION: Primary surgical exploration of the biliary tract without previous biopsy was effective at improving the prognostic indicators of patients with biliary atresia undergoing Kasai portoenterostomy.

The role of interleukin-6, endothelins, and apoptotic genes in small bowel transplantation, in a swine model of ischemia and reperfusion injury.

IRI is closely related to sepsis in ITx setting. Complete understanding of the mechanisms involved in IRI development may improve outcomes. Ortothopic ITx without immunosuppression was performed in order to characterize IRI-associated mucosal damage. Twenty pigs underwent ITx. Two groups were assigned to different CI times: G1: 90 min and, G2: 180 min. Euro-Collins was used as preservation solution. Jejunal fragments were collected at donor laparotomy, 30 min, and 3 days after reperfusion. IRI assessment involved: histopathologic analysis, quantification of MPO-positive cells through immunohistochemical studies, quantification of epithelial apoptotic cells using TUNEL staining, and quantification of IL-6, ET-1, Bak, and Bcl-XL genes expression by RT-PCR. Neutrophilic infiltration increased in a similar fashion in both groups, but lasted longer in G2. Apoptosis detected by TUNEL staining increased and anti-apoptotic gene Bcl-XL expression decreased significantly in G1, 3 days after surgery. Endothelin-1 and IL-6 genes expression increased 30 min after the procedure and returned to baseline 3 days after surgery. In conclusion, IL-6 and ET-1 are involved precociously in the development of intestinal IRI. Apoptosis was more frequently detected in G1 grafts by TUNEL-staining and by RT-PCR.

Extrahepatic portal vein thrombosis after umbilical catheterization: is it a good choice for Rex shunt?

BACKGROUND: Extrahepatic portal vein thrombosis (EHPVT) is an important cause of portal hypertension in children. Rex shunt has been used successfully to treat these patients. METHODS: We report our experience in 19 infants and children (5 months to 14 years) with HPVT eligible for a mesenteric-portal surgical shunt with left internal jugular vein autograft. Eight children had idiopathic EHPVT, nine had post-umbilical catheterization EHPVT, one had portal vein agenesis, and one had posttransplant EHPVT. RESULTS: It was possible to perform the Rex shunt in all patients except for 8 of 9 cases in the post-umbilical catheterization EHPVT group. A Warren procedure was performed in 4 of those patients and a proximal splenorenal shunt in 1. Current follow-up ranges from 3 to 26 months. Shunt thrombosis occurred in one patient with portal vein agenesis and associated cardiac anomaly. Portal hypertension has significantly improved after surgery. None of our patients have experienced new bleeding episodes until now. CONCLUSIONS: The Rex shunt should be considered in the treatment of children with idiopathic EHPVT experiencing repeated gastrointestinal bleeding episodes refractory to endoscopic treatment. Nevertheless, the role of this operation for children with post-umbilical catheterization EHPVT is yet to be clearly evaluated.

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation.

PURPOSE: Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. METHODS: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. RESULTS: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors-4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors (P = .04). CONCLUSION: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate.

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.

Bile duct ligation in neonatal rats: is it a valid experimental model for biliary atresia studies?

BA is the most important disease requiring liver transplantation in children. Common BDL in rats is a classic experimental model to study biliary obstruction. The response of the neonatal animal to BDL has yet to be completely understood and few reports have focused on the behavioral differences of the liver between neonatal and adult animals. Ninety newborn Wistar rats aged six days, weighing 8.0-13.9 g, and 90 adult Wistar rats weighing 199.7-357.0 g, were submitted to BDL. After surgery, they were randomly divided and killed on the 3rd, 5th, 7th, 14th, 21st and 28th day post-BDL. Hepatic biopsies were obtained and the following were measured: (i) semiquantification of the bile ductule proliferation and inflammatory infiltrate by HE stain, (ii) quantification of portal and periportal fibrosis with the Sirius-red stain. Although the initial response of ductule proliferation and inflammatory infiltrate were less intense in the newborn animal, the portal and periportal fibrosis were higher when compared with adult animals (p < 0.0491). These findings may contribute to the understanding of the pathophysiology of BA.

Immunohistochemical studies of stellate cells in experimental cholestasis in newborn and adult rats.

BACKGROUND AND AIMS: Although there is much known about liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases observed in newborn infants and those in adults. For example, how do newborns respond to duct epithelial cell injury? Do the stellate cells in newborns respond similarly to those in adults during biliary obstruction? METHODS: Ninety newborn Wistar rats aged six days, weighing 8.0 - 13.9 g each, and 90 adult rats weighing 199.7 - 357.0 g each, were submitted to bile duct ligation. After surgery, they were randomly divided and sacrificed on the 3rd, 5th, 7th, 14th, 21st or 28th day post-bile duct ligation. Hepatic biopsies were obtained and immunohistochemical semi-quantification of desmin and alpha-SMA expression was performed in hepatic stellate cells and in myofibroblasts in the portal space, and between the portal space and the liver lobule. RESULTS: Desmin expression in the myofibroblast cells post-bile duct ligation was higher in young rats, reaching its peak level in a shorter time when compared to the adult animals. The differences between the groups for alpha-SMA expression were less significant than for desmin. CONCLUSIONS: These findings indicate that there is an increase in the number of collagen-producing myofibroblast cells in young animals, suggesting that there is more intense fibrosis in this population. This finding may explain why young animals with bile duct obstruction experience more intense portal fibrosis that is similar to the pathology observed in the livers of newborns with biliary atresia.

Intimal dissection of the hepatic artery after thrombectomy as a cause of graft loss in pediatric living-related liver transplantation.

HAT is the main cause of graft loss in pediatric living-related LTx. Revascularization of the graft by thrombectomy and re-anastomosis has been reported to be effective for graft salvage in cases of HAT and should be attempted when potential donors are not available for emergency re-transplantation. Immediate complications secondary to revascularization attempts in cases of HAT are not described. Late complications are mainly related to biliary tree ischemia. We report a case of child who experienced intimal hepatic artery dissection, which extended into intra-hepatic branches of the artery after a thrombectomy with a Fogarty balloon catheter in an attempt to restore arterial flow after HAT. This complication led to acute deterioration of the graft and the need for emergency re-transplantation.

Immunohistochemical studies of stellate cells in experimental cholestasis in newborn and adult rats

BACKGROUND AND AIMS: Although there is much known about liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases observed in newborn infants and those in adults. For example, how do newborns respond to duct epithelial cell injury? Do the stellate cells in newborns respond similarly to those in adults during biliary obstruction? METHODS: Ninety newborn Wistar rats aged six days, weighing 8.0 - 13.9 g each, and 90 adult rats weighing 199.7 - 357.0 g each, were submitted to bile duct ligation. After surgery, they were randomly divided and sacrificed on the 3rd, 5th, 7th, 14th, 21st or 28th day post-bile duct ligation. Hepatic biopsies were obtained and immunohistochemical semi-quantification of desmin and á-SMA expression was performed in hepatic stellate cells and in myofibroblasts in the portal space, and between the portal space and the liver lobule. RESULTS: Desmin expression in the myofibroblast cells post-bile duct ligation was higher in young rats, reaching its peak level in a shorter time when compared to the adult animals. The differences between the groups for á-SMA expression were less significant than for desmin. CONCLUSIONS: These findings indicate that there is an increase in the number of collagen-producing myofibroblast cells in young animals, suggesting that there is more intense fibrosis in this population. This finding may explain why young animals with bile duct obstruction experience more intense portal fibrosis that is similar to the pathology observed in the livers of newborns with biliary atresia.

Fibrose portal e periportal na obstrução extra-hepática experimental em ratos jovens e adultos: contribuição para o estudo da atresia das vias biliares / Portal and periportal fibrosis in experimental extra-hepatic biliary obstruction in young and adult rats

A atresia das vias biliares é afecção hepática da infância. A etiologia é desconhecida, e o diagnóstico baseia-se na biópsia hepática, cujo achado é a proliferação ductular. A ligadura do ducto biliar comum em ratos é modelo utilizado para estudo das doenças colestáticas. A proposta do trabalho foi estudar, em modelo experimental de obstrução biliar, as alterações histológicas hepáticas em ratos jovens e compará-las com o animal adulto / Biliary atresia is an hepatic disease of infancy. Etiology is unknown, and diagnosis is made by liver biopsy, with ductular proliferation being the main histological feature. Bile duct ligation in rats is an useful experimental model of biliary obstruction. The aim of this study of extra-hepatic cholestasis was analyse hepatic histological alterations in young rats compared to adult animals...