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Riccardo A Superina

Publications and source records attributed to Riccardo A Superina.

17 recordsLinked to original sources
PubMed2006

Gene transfer of pigment epithelium-derived factor suppresses tumor growth and angiogenesis in a hepatoblastoma xenograft model.

Normal hepatocytes express pigment epithelium-derived factor (PEDF), an endogenous antiangiogenic factor. We hypothesized that decreased PEDF expression may be one mechanism driving hepatoblastoma growth, and in vivo gene transfer of PEDF could suppress neovascularization and limit tumor growth. PEDF functional activity was determined in vitro using endothelial cell migration assays and in vivo using a subcutaneous tumor model. HUH-6 human hepatoblastoma tumors were treated with hybrid adenoviral/adeno-associated viral expression vectors for PEDF (Hyb-PEDF, n = 4) or beta-galactosidase (Hyb-betagal, n = 4) daily for 4 d. Mitotic figures, microvascular density (MVD), PEDF, and VEGF expression were assessed. Hyb-PEDF treatment inhibited in vivo tumor growth (p < 0.008) and decreased MVD (p < 0.001), the number of mitotic figures (p < 0.001), and VEGF expression when compared with Hyb-betagal-treated tumors. HUH-6 expression of PEDF was dramatically reduced when cultured under hypoxic conditions and also when grown in vivo, and the addition of neutralizing anti-PEDF antibody increased the already high baseline angiogenic activity of the HUH-6 cell secretions in vitro (p < 0.04). PEDF is an important endogenous regulator of the liver vasculature. Augmenting intra-tumoral PEDF levels inhibits tumor growth by reducing angiogenesis and VEGF expression. Potent inhibitors of angiogenesis, such as PEDF, may be an effective alternative treatment for children with hepatoblastoma.

Animals↗
PubMed2006

Outcomes and risk factors for failure of radiologic treatment of biliary strictures in pediatric liver transplantation recipients.

Posttransplantation biliary strictures occur in 5-34% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. The aim of this manuscript is to assess the outcomes of patients with biliary strictures treated by percutaneous dilatation at our institution. Included in the study were 35 children with posttransplant biliary strictures that were treated with percutaneous dilatation and stenting. Initial dilation and biliary stent placement was accomplished in all patients without complications requiring surgical intervention. Recurrent strictures developed in 23 (66%) of 35 patients. The recurrence rate was 45% for anastomotic strictures, 90% for intrahepatic strictures, and 100% for those with both an anastomotic and intrahepatic component. Seven patients required revision of the choledochojejunostomy, 5 of them with a successful outcome and 2 requiring retransplant. Five patients were treated with retransplantation without surgical revision. Patients with an intrahepatic or a "combined" stricture were less likely to have a successful outcome after radiologic treatment. In conclusion, the radiological treatment of biliary strictures with balloon dilation and stenting can be performed successfully with minimal complications avoiding the need for surgical correction in many cases.

Adolescent↗
PubMed2006

Medical and surgical management of portal hypertension in children.

The treatment of portal hypertension in children has undergone considerable evolution in the past decade. The treatment offered depends on the cause of the hypertension and the underlying health of the liver. The diagnosis of portal hypertension often can be made by the history and physical examination. Upper gastrointestinal bleeding in the presence of splenic enlargement is pathognomonic for portal hypertension. Bleeding and hypersplenism are the principal symptoms. Treatment of bleeding starts with confirming the diagnosis with esophageal and gastric endoscopy. The patient is admitted to an intensive care unit and started on intravenous octreotide. Banding or sclerosis of esophageal varices will result in cessation of the bleeding but not a permanent cure. A careful investigation for the cause of the portal hypertension should be done. This includes imaging studies of intra-abdominal arteries and veins, a liver biopsy, and liver function tests, including coagulation studies. For patients with extrahepatic portal vein thrombosis, early consideration should be given to surgical treatment with a meso-Rex bypass. Patients with liver disease should be treated for the underlying disorder and undergo regular endoscopic monitoring for recurrence of varices. Patients with well-compensated cirrhosis should be considered for selective surgical shunting, and those with advanced disease for liver transplantation. The benefit of long-term beta blockers in children has not been proven by clinical trials.

Journal Article↗
PubMed2006

Effectiveness of Rex shunt in the treatment of portal hypertension.

BACKGROUND: Children with portal venous thrombosis often have severe symptoms secondary to portal hypertension including recurrent upper gastrointestinal (UGI) bleeds and hypersplenism. We report results of the use of the mesenterico-left portal bypass (Rex shunt) in 5 consecutive patients. METHODS: A retrospective chart review of all patients with portal venous thrombosis who underwent Rex shunt procedure was performed. Children were evaluated preoperatively with magnetic resonance angiogram, Doppler ultrasound, and mesenteric angiogram. Postoperative ultrasounds were performed in follow-up. RESULTS: All patients had evidence of portal hypertension and hypersplenism. The average age of the patients was 13.2 +/- 4.9 (7-19) years. The patient had an average of 2.6 +/- 1.7 UGI bleeds requiring banding and 3.4 +/- 4.2 U of blood transfused before undergoing the shunt. The mean operative time was 383 +/- 46 minutes, and length of stay was 10.4 +/- 7.1 days. In follow-up of 18.8 +/- 5.2 months (11-24 months), all but 1 patient had a patent shunt. One narrowed shunt was successfully dilated by percutaneous angioplasty. Thrombocytopenia improved significantly in patients with functioning shunts but did not correlate with a significant decrease in splenic size. CONCLUSIONS: The Rex shunt reestablishes normal hepatopedal portal flow, and in patients with functioning shunts, no recurrent UGI bleeds or transfusions were required or evidence of encephalopathy were noted.

Adolescent↗
PubMed2006

Longitudinal pancreaticojejunostomy and selective biliary diversion for chronic pancreatitis in children.

BACKGROUND: Chronic pancreatitis requiring surgery is rare in children. We review our experience in treating pediatric chronic pancreatitis with longitudinal pancreaticojejunostomy (LPJ). METHODS: Records of children with chronic pancreatitis treated with LPJ between 1997 and 2003 were reviewed. Demographic data, associated conditions, endoscopic interventions, operative procedures, postoperative complications, length and costs of hospitalization, and long-term outcome were recorded. RESULTS: Four patients (one girl), 3 to 16 years old, underwent LPJ. Associated conditions included bile duct obstruction (2), single (1) or multiple (1) pancreatic duct strictures, recurrent familial pancreatitis (1), pseudocyst (1), Down's syndrome (1), and duodenal web (1). Preoperative endoscopic stenting was performed in two patients. All were on restricted diets, one on parenteral nutrition. Pre-LPJ, each child had 3 to 6 admissions for pancreatitis with mean total cost of 39,000 dollars, excluding diet charges. At surgery, two patients required biliary diversion for persistent biliary obstruction in addition to LPJ. Postoperatively, no patient developed fistulas or anastomotic leaks. There were no deaths. The median length of hospitalization post-LPJ was 8 days with mean cost of US37,000 dollars. All patients resumed a normal diet post-LPJ. There were no recurrences of pancreatitis with follow-ups between 2 and 6 years. CONCLUSION: Longitudinal pancreaticojejunostomy is safe and cost-effective for treating pediatric chronic pancreatitis. It has minimal complications and frees patients from pancreatitis-related hospitalizations.

Adolescent↗
PubMed2006

Encephalopathy caused by a splenorenal shunt can be reversed by performing a mesenteric-to-left portal vein bypass.

Surgically created portosystemic shunts can alleviate the symptoms of bleeding from gastric and esophageal varices and improve the hematologic consequences of hypersplenism in patients with portal hypertension. However, the diversion of mesenteric venous blood away from the liver can result in encephalopathy. In this report, we describe a case in which encephalopathy caused by a proximal splenorenal shunt was reversed by the restoration of portal flow to the liver by a mesenteric-to-left portal vein bypass operation.

Adolescent↗
PubMed2005

Liver graft volume estimation in 100 living donors: measure twice, cut once.

Estimation of graft volume (GV) is critical in living donor liver transplantation. This study examines the accuracy of formula-derived GV estimates and compares them to both radiogically-derived estimates and actual measurements. We first compared formula-derived estimates of GV and compared them to actual volumes to provide estimates for both right lobe (RL) and left lateral segment (LLS) GV. We then applied these formulae to a validation cohort. Finally, we evaluated both formula-derived and radiologically-derived estimates by comparing them to actual GV measurements. There is a marginal concordance between formula-derived calculation and GV for RL donors, but the error ratio was lower than for radiologic estimates. In contrast, MRI measurements for LLS grafts demonstrated a lower error ratio than formula-derived estimation. Formula-derived estimates of GV should be routinely used in the initial screening of potential living donors as long as their limitations are appreciated.

Biometry↗
PubMed2005

Presence of multiple bile ducts in the liver graft increases the incidence of biliary complications in pediatric liver transplantation.

We studied the impact of multiple bile duct anastomosis on the development of biliary complications after liver transplantation in children. A total of 101 patients received a primary liver transplant and were divided into 2 groups: those with a single bile duct (n = 77) and those with multiple bile ducts (n = 24). Mean follow-up was 39.8 +/- 20.8 months. A total of 27 patients presented with biliary complications (26.7%), 18 patients (18.7%) presented with early complications (12 leaks and 6 strictures), and 9 patients (8.9%) had late strictures. Hepatic artery thrombosis (HAT) and multiple bile ducts were significant risk factors for the development of biliary complications, and the presence of multiple bile ducts was an independent risk factor. Patients with multiple bile ducts had a significantly greater incidence of total biliary complications compared to those with single ducts. Patients with multiple ducts had a higher incidence of leaks when compared to those in the single duct group, but the incidence of strictures, both early and late, was similar in both groups. One-year patient and graft survivals were not statistically different in the 2 groups. In conclusion, the presence of more than one bile duct in the graft is an independent risk factor for the development of biliary complications after pediatric liver transplantation.

Anastomosis, Surgical↗
PubMed2005

Management of an epidermoid cyst of the intrahepatic ducts.

Epidermoid cysts of the biliary tree have not previously been described. A baby boy presented with a prenatally diagnosed echolucent intrahepatic cyst. Postnatal radioisotope study of the liver demonstrated that the cyst communicated with the biliary tree. Follow-up ultrasound at 6 months demonstrated that the cyst was filled with echogenic material consistent with either blood or biliary debris. Due to the potential for obstruction and cholangitis, surgery was planned. The cyst was located at the confluence of the right and left hepatic ducts and involved all of the common hepatic duct. The entire cyst was resected except for the patch containing 3 duct orifices: the opening of both hepatic ducts as well as the orifice leading to the common bile duct. A Roux-en-Y cyst jejunostomy was created to allow drainage of both left and right hepatic ducts. The connection also provided access to the cyst remnant through the common duct for future endoscopic monitoring of potential malignant transformation.

Anastomosis, Roux-en-Y↗
PubMed2005

Regional variation and use of exception letters for cadaveric liver allocation in children with chronic liver disease.

The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce subjectivity in liver allocation and to advantage patients with a higher probability of waiting list mortality. The aims of this study were to determine the impact of PELD implementation for children with chronic liver disease and to assess whether PELD met its goal of standardization of liver allocation for children. This study used data reported to the United Network for Organ Sharing (UNOS) registry for children with chronic liver disease receiving primary cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and March 2002 and July 2003 (PELD). PELD reduced the percentage of children transplanted while in an intensive care unit and as status 1. A calculated PELD score was used for allocation in only 52% of recipients. Thirty percent were status 1 at transplant and PELD scores granted by exception were used for allocation in 18% of patients. There was regional variation in PELD score at allocation and use of exception scores with a significant relationship between PELD score and percentage of exception cases. Regional variation suggests that PELD has not resulted in standardization of listing practices in pediatric liver transplantation.

Cadaver↗
PubMed2004

Comparative analysis of live liver donation risk using a comprehensive grading system for severity.

We investigated whether right lobe (RL) liver donation is associated with a higher incidence or severity of donor complications than left lobe (LL) liver and left lateral segment (LLS) liver donations. We studied 80 living donors: 35 RL liver donors and 45 LL/LLS liver donors. A modification of the Clavien classification was used to grade the severity of complications. RL and LL/LLS liver donations had equivalent blood loss, readmission and reoperation rates, use of blood products, and lengths of stay in the intensive care unit and hospital. RL liver donors underwent longer surgeries and experienced more postoperative pain than LL/LLS liver donors. The overall rate of complications was 33%. There was a higher rate of complications in RL liver donors (51%) than LL/LLS liver donors (20%). When graded by severity, there were more grade 2 complications in RL liver donors than in LL/LLS liver donors. Our report confirms that RL liver donation is associated with higher morbidity than LL/LLS liver donation. When the complications are systematically graded by severity, there is a significant difference in Clavien grade 2 complications in RL liver donors.

Adult↗
PubMed2004

Simultaneous surgical and interventional radiological approach to treat complicated biliary strictures after pediatric liver transplantation.

Post-transplantation biliary strictures occur in 5-15% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. Failure of this treatment leads to reoperation and sometimes to retransplantation. Herein, we describe a surgical approach and interventional radiologic approach to manage biliary strictures that failed the conventional radiologic treatment, in order to avoid retransplantation. Included in the study were eight children who underwent liver transplantation at our center or referred to our institution for evaluation of the biliary strictures that failed radiological treatment. Biliary strictures were confirmed by a narrowing of the biliary anastomosis on the percutaneous transhepatic cholangiogram. At surgery, a guide wire was introduced into the distal bile system through the use of an enterotomy in Roux limb. Over the guide wire, the stricture was ballooned and the diameter of the biliary tree was determined. A pigtail catheter was introduced on the biliary tree across the abdominal wall, the liver, the stricture and the anastomosis into the enterotomy. A final cholangiogram confirmed the positioning of the catheter. Mean follow-up was 39.8 +/- 20.8 months. All patients had their strictures successfully treated and survived the procedure. Three patients were readmitted to the hospital with fever. It was necessary to revise the hepaticojejunostomy in three patients because of cholangitis and/or recurrence of biliary stricture. Of the eight patients of this study, two required retransplantation and one died. We conclude that an aggressive combined surgical and radiologic approach can avoid retransplantation in patients with complicated post-transplant biliary strictures.

Bile Ducts↗
PubMed2003

Abnormalities in villin gene expression and canalicular microvillus structure in progressive cholestatic liver disease of childhood.

BACKGROUND: The molecular basis of clinical cholestasis is a subject of intense investigation. Villin is an actin binding, bundling, and severing protein needed for maintenance of structural integrity of canalicular microvilli, in which membrane transporters required for bile secretion are located. We aimed to investigate the role of canalicular cytoskeletal proteins in three genetically unrelated children with a biliary atresia-like clinical disorder, each of whom developed liver failure requiring liver transplantation. METHODS: Explanted livers from the three patients were examined by standard pathological methods followed by transmission and cryoimmunoelectron microscopy. With archival tissue samples, a panel of cytoskeletal proteins was investigated by immunohistochemistry and western blotting, with purified canalicular membrane preparations. Villin mRNA analyses were undertaken on liver homogenates, with primers from coding regions of the human villin gene. Classic biliary atresia, other types of cholestasis, and normal livers served as controls. FINDINGS: In patients, pronounced ultrastructural deformities of canaliculi and especially of their microvilli were noted, which correlated with absence of villin protein by immunostaining of liver tissue sections and by western blot analysis. Additionally, villin mRNA was strikingly reduced or absent. These results differed greatly from those in controls. INTERPRETATION: These results suggest that the disorder described mimics biliary atresia, but structural and molecular pathological findings differ. We propose that a functional abnormality in villin gene expression is key to the mechanism of cholestasis in patients with progressive cholestasis and hepatic failure.

Biliary Atresia↗
PubMed2003

Surgical restoration of portal flow corrects procoagulant and anticoagulant deficiencies associated with extrahepatic portal vein thrombosis.

Extrahepatic portal vein thrombosis (EHPVT) is associated with abnormal circulating procoagulants and anticoagulants. Eleven children with EHPVT and abnormal coagulation factors underwent a mesenterico-left portal vein bypass to restore portal flow. Coagulation factors had returned to normal by one year. The data suggest that portal venous flow is essential for maintaining normal coagulation.

Antithrombin III↗
PubMed2002

Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride.

BACKGROUND: Efficiency of engraftment after liver cell transplantation is less than 1% under conventional conditions. Our aim was to develop a high-efficiency, nonsurgical, no-genetic-advantage mouse model of liver repopulation with transplanted cells. METHODS: Mice were conditioned with nonlethal doses of a cell cycle inhibitor, retrorsine, 70 mg/kg, to irreversibly block proliferation of native hepatocytes. After the drug was eliminated, 2 million freshly isolated beta-galactosidase-labeled liver cells were transplanted into the spleens of C57BL/6J recipient mice. To stimulate donor cell proliferation, three doses of carbon tetrachloride (CCl4), 0.5 ml/kg, were given. Several control groups were studied to evaluate the contribution of each treatment to liver repopulation. RESULTS: Repopulation, as measured by cell isolation from recipient livers 1-7 months after transplantation, was on average 20%. Repopulation was 10% if CCl4 was given only once, between 0.5% and 1% if only retrorsine or CCl4 were used, and 0.05% if no conditioning was used. Phenotypically, whole livers turned blue on exposure to X-gal staining, whereas negative (control) livers remained pale brown. More than 55% of liver repopulation resulted from clusters containing 21 or more cells, some of which contained more than 200 cells, suggesting seven or more rounds of cell division in a subset of transplanted cells. CONCLUSION: This murine study demonstrates high levels of repopulation after liver cell transplantation into nongenetically modified livers, using a cell cycle inhibitor and chemical liver injury to provide transplanted cells a proliferative advantage. Liver repopulation was effected mostly by a small fraction of transplanted cells. Analogous nonsurgical liver cell transplantation strategies, but with clinically applicable drugs, could be devised for the treatment of liver-based metabolic diseases.

Animals↗