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The meso-Rex bypass is a physiological and anatomical bypass procedure for relief of extrahepatic portal vein obstruction and restoration of mesenteric venous return to the liver. Most patients who are candidates for the bypass are children or young adults with portal hypertension and hypersplenism secondary to cavernous transformation of the portal vein. Most frequently, the bypass utilizes an autologous venous graft to connect the intrahepatic left portal vein to the infrapancreatic superior mesenteric vein (SMV) re-establishing first-pass portal perfusion. We describe the preoperative imaging of the 92 bypass candidates, the surgical anatomy as reflected in postoperative imaging, and the imaging of bypass complications at our institution. Preoperative imaging with US, CT and MR is directed to demonstrate patency and size of the left portal vein and SMV, to define the extent of cavernous transformation and splanchnic collaterals, and to assess for any associated abdominal vascular or solid organ abnormalities. Postoperative imaging is aimed at diagnosing meso-Rex bypass stenosis or occlusion and the interventional management of these complications.

Background/Purpose Extrahepatic portal vein obstruction (EHPVO) is an important cause of chronic portal hypertension in children. Although usually idiopathic in etiology, genetic and acquired thrombophilia have been implicated in EHPVO. Meso-Rex bypass is increasingly used to treat EHPVO in children. Objective The objective of this study is to assess the relationship of postoperative anticoagulation strategies and thrombophilic risk factors to the development of bypass thrombosis following the meso-Rex bypass. Methods Records of children who underwent meso-Rex bypass for EHPVO at a single institution from 1999 to 2009 were reviewed, and preoperative thrombophilia testing, perioperative anticoagulation strategies, and postoperative bypass patency based on imaging at last follow-up were examined. Results Sixty-five children with EHPVO underwent a first time meso-Rex bypass during the study period, and 9 of 65 (14 %) developed bypass thrombosis. The use of warfarin in the postoperative period was more common among children with thrombosed shunts than among those with open shunts [63 % vs. 20 %; OR, 6.5 (95 % CI, 1.3–31.5), p  = 0.022]. The contribution of genetic or acquired thrombophilia to shunt thrombosis was inconclusive given variability in testing. Conclusions Choice of anticoagulation following meso-Rex bypass may affect postoperative incidence of bypass thrombosis. Role of thrombophilic risk factors in the development of shunt thrombosis remains unclear.

BackgroundThe meso-Rex bypass restores blood flow to the liver in patients with extrahepatic portal vein thrombosis. Stenosis occurs in some cases, causing the reappearance of portal hypertension. Complications such as thrombocytopenia present on a spectrum and there are currently no guidelines regarding a threshold for endovascular intervention. While Doppler ultrasound (US) is common for routine evaluation, magnetic resonance (MR) angiography with two-dimensional phase-contrast MRI (2-D PC-MRI) may improve the assessment of meso-Rex bypass function.ObjectivesTo determine the feasibility and utility of MR angiography with 2-D PC-MRI in evaluating children with meso-Rex bypass and to correlate meso-Rex bypass blood flow to markers of portal hypertension.Materials and methodsMR angiography and 2-D PC-MRI in meso-Rex bypass patients were retrospectively analyzed. Minimum bypass diameter was measured on MR angiography and used to calculate cross-sectional area. Meso-Rex bypass blood flow was measured using 2-D PC-MRI and divided by ascending aortic flow to quantify bypass flow relative to systemic circulation. Platelet and white blood cell counts were recorded. Correlation was performed between minimum bypass area, blood flow and clinical data.ResultsTwenty-five children (median age: 9.5 years) with meso-Rex bypass underwent MR angiography and 2-D PC-MRI. The majority of patients were referred to imaging given clinical concern for complications. Eighteen of the 25 patients demonstrated >50% narrowing of the bypass cross-sectional area. The mean platelet count in 19 patients was 127 K/μL. There was a significant correlation between minimum cross-sectional bypass area and bypass flow (rho=0.469, P=0.018) and between bypass flow and platelet counts (r=0.525, P=0.021).ConclusionTwo-dimensional PC-MRI can quantify meso-Rex bypass blood flow relative to total systemic flow. In a cohort of 25 children, bypass flow correlated to minimum bypass area and platelet count. Two-dimensional PC-MRI may be valuable alongside MR angiography to assess bypass integrity.

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. 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. 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. 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.

Profound thrombocytopenia resulting from portal hypertension may exacerbate gastrointestinal bleeding, precipitate spontaneous bleeding, preclude surgical intervention for associated disorders, and severely limit life-style because of the danger of splenic injury. Although splenectomy can reverse the thrombocytopenia, the procedure should be avoided in children. We reviewed our experience with distal splenorenal shunting (DSRS) in children, particularly when performed for the sole purpose of reversing severe thrombocytopenia resulting from portal hypertension. DSRS was performed in 11 children between the ages of 7 and 15 years: five for severe thrombocytopenia (group 1), four for advanced hypersplenism and congenital hepatic fibrosis prior to renal transplantation (group 2), and two for esophageal bleeding (group 3). One child in group 1 with severe heart disease and Child's class C cirrhosis due to hepatitis C died of progressive cardiac failure and was excluded from further analysis. Of the eight remaining patients in groups 1 and 2, four children had congenital hepatic fibrosis, two had portal vein thrombosis, one had hepatitis B, and one had Wilson's disease. After DSRS, the mean platelet count increased from 37,000 ± 18,000 to 137,600 ± 81,000 ( P = 0.01). The platelet count improved significantly in all seven children with presinusoidal portal hypertension or stable cirrhosis but did not increase in the child with hepatitis B and Child's class B cirrhosis. The white blood cell count increased from an average of 3.3 ± 1.1 to 5.4 ± 2.6 ( P = 0.02). There were no postoperative complications in this group. The improved platelet count allowed the four children with congenital hepatic fibrosis and renal failure to undergo renal transplantation with full posttransplant immunosuppression including azathioprine. Postoperative Doppler ultrasound examination demonstrated shunt patency at 6 months in all cases. Spleen size decreased appreciably in all children in groups 1 and 2. All children were able to resume full activity including contact sports. In summary, DSRS effectively controls profound thrombocytopenia resulting from presinusoidal portal hypertension or stable cirrhosis without sacrificing the spleen and should be the treatment of choice for this condition.

IN this paper, we describe 10 patients seen over a six-year period with acute and chronic hepatitis in whom liver-biopsy specimens were characterized by the presence of giant multinucleated syncytial hepatocytes. Giant cells are a common pathological finding in liver disorders in infants and very young children, but they are not common in adults. Large syncytial giant hepatocytes have rarely been described in patients at any age, and their association with intracytoplasmic structures consistent with paramyxoviral nucleocapsids, found in 8 of the 10 cases reported here, has never to our knowledge been described. The clinical and pathological features of this . . .

Immunological unresponsiveness to allografts can be achieved by pretreating recipients with cells (whole blood, erythrocytes, lymphocytes) expressing donor-specific histocompatibility antigens. Attempts to determine the relative contribution of class I or class II major histocompatibility antigens and/or minor histocompatibility (miH) antigens towards the induction of an unresponsive state have yielded conflicting results. We have addressed this issue using DNA-mediated gene transfer to introduce murine class I or class II major histocompatibility complex (MHC) genes from the organ donor into cells of recipient origin. This allowed murine recipients of cardiac allografts to be pretreated with either donor cells sharing only an isolated class I or class II MHC locus product with the donor organ. We show that pretreatment with either donor class I or class II antigens prolongs survival of cardiac allografts, and that the capacity of a particular donor MHC antigen to induce unresponsiveness is the product of its intrinsic immunogenicity and the antigen load delivered during pretreatment. These results explain discrepancies in earlier studies of antigen-induced unresponsiveness and suggest a novel approach to specific immunosuppression in clinical transplantation.

Summary Background High hepatic copper concentrations have been reported in several liver disorders. We report six Native Canadian children with severe chronic cholestatic liver disease, who had excess hepatic copper and zinc. Methods The children, aged 22 months to 8 years, came from northern Ontario, Canada. All were referred for possible liver transplantation because of end-stage liver disease. We examined explanted liver samples (or liver biopsy material in one case) by scanning transmission electronmicroscopic (STEM) X-ray elemental microanalysis and atomic absorption spectrophotometry. Samples from four controls (two with no liver pathology, one with biliary atresia, and one with Wilson's disease) were also analysed by atomic absorption spectrophotometry. Findings The explanted livers showed similar distinctive signs of advanced biliary cirrhosis, and on electron-microscopy there were dense deposits in enlarged lyosomes and in cytoplasm. Hepatic copper concentrations were many times higher in the five patients with measurements (47·6-56·9 μg/g dry weight) than in two samples of normal control liver tissue (2·3 and 2·9 μg/g). Similarly, hepatic zinc concentrations were many times higher in the patients than in controls (104-128 vs 1·9-3·2 μg/g dry weight). Interpretation The excess copper may be due to chronic cholestasis but the excess zinc is unexplained. Since three of the patients are related (shared grandparents), a genetic disorder of metal metabolism is possible, but we cannot exclude environmental factors.

Biliary atresia (BA) is one of the most common indications for liver transplantation in children. Despite advances in biliary atresia surgical techniques, most children will ultimately require liver transplantation. Possible pre-operative predictors of outcome after the Kasai operation are: 1. Age at operation 2. Presence of the biliary atresia splenic malformation syndrome (BASM) 3. Center specific factors 4. Liver histology and 5. Anatomic pattern of bile ducts found at surgery. Age at surgery is considered a strong predictor of success after portoenterostomy. In a recent study, age of 75 days or more at surgery was associated with less frequent resolution of jaundice and decreased transplant free survival. Similarly, the Ohi type II or III anatomy was associated with a higher risk of transplantation or death than type I. Inflammatory findings on pre-operative biopsy predicted a pooreroutcome after a Kasai procedure than obstructive changes. Nodularity of the liver at surgery as well as ascites was associated with a poorer prognosis. Primary transplantation is rarely done despite excellent outcome. Deaths on the waiting list also have improved with routine use of split and live donor transplantation. The Kasai operation has the highest failure rate in its stated objective than any other operation in pediatric surgery. Failure to achieve any improvement in jaundice occurs in over 30% of all cases, even in the best of hands, and transplantation or listing for transplantation occurs in over half the children with type II and III BA by one year of age in countries where liver transplantation is readily available. There are almost no studies in children with BA that compare the outcome after liver transplantation for BA with or without a prior Kasai procedure. It is postulated that a prospective trial in children predicted to have a poor prognosis after the Kasai procedure based on anatomic pattern, liver histology and presence of BASM, would yield improved care, spare some infants needless surgery, and quite possibly result in diminished morbidity and mortality following liver transplant.