Surgical complications and outcome of paediatric liver transplantation: the Singapore experience

The purpose of this study was to analyse the early and late results of paediatric liver transplantation (LT), with particular reference to complications that required surgical intervention. The charts of all children who underwent LT between 1990 and 2002 were reviewed retrospectively. Results were analysed with a minimum follow up of 9 months. Thirty-five children have undergone 38 LTs; 22 received grafts from their parents, 16 received cadaveric organs and three children had retransplantation. The ages of the children ranged from 12 to 168 months. Biliary atresia was the most frequent indication for transplant (n=27). Twenty-seven children had complications that required surgical or radiological interventional procedures. Vascular complications included hepatic artery thrombosis (n=2), hepatic vein (HV) thrombosis (n=1), and the majority being portal vein thrombosis (n=6). Bile leaks were observed in eight children. Other complications included intestinal perforation (n=2), intra-abdominal abscesses (n=1), wound dehiscence (n=2), post-operative bleed (n=2), intestinal obstruction (n=2), ventral hernia (n=1), and multiple abdominal wound sinuses (n=1). Three children underwent retransplantation, two for hepatic artery thrombosis with multiple episodes of cholangitis and intrahepatic biliomas and the third was done for hepatic vein thrombosis. Patient and graft survival at 1 year is 81.5 and 74.2%, respectively. Paediatric LT is associated with significant morbidity, the main complications being vascular and biliary. The article was presented at the 8th Congress of the Asian Society of Transplanatation (8th CAST) in September 2003 held in Kuala Lumpur, Malaysia.     

Aberrant patterns of cellular communication in diabetes-induced embryopathy in rats: II, apoptotic pathways

OBJECTIVE: The objective was to test the hypothesis that hyperglycemia-induced injury of yolk sac cell membranes is associated with disruption of cellular apoptotic signaling pathways. STUDY DESIGN: Pregnant rats were induced to become diabetic by injection of streptozotocin. Fourteen normal control and 24 diabetic rats were killed on day 12 of gestation. Yolk sac membranes in 3 conceptus groups (nondiabetic, diabetic with normal, or diabetic with malformed conceptus) were collected for study. DNA was extracted from yolk sac cells and assayed for fragmentation by using gel electrophoresis, which indicates apoptosis. Protein expression was evaluated by Western blot assays. Statistical analyses were performed with the Student t -test. RESULTS: The level of phosphorylated Akt was significantly decreased, whereas that of the proapoptotic protein Bax was increased. These changes were correlated with the presence of DNA fragmentation in yolk sac cells of the diabetic malformed conceptuses. CONCLUSION: Hyperglycemia-induced embryopathy involves apoptosis, during which the expression of proapoptotic protein Bax is upregulated and the activity of the cell-survival factor, Akt kinase, is decreased in yolk sac cells. These observations suggest that hyperglycemia of maternal diabetes triggers apoptotic signaling pathways and inhibits cell survival pathways, leading to embryonic malformations.     

Overwhelming leukoencephalopathy as the only sign of neuropsychiatric lupus

We describe a patient with diffuse leukoencephalopathy, a rare central nervous system complication of systemic lupus erythematosus, who died of brain herniation despite aggressive management. Brain magnetic resonance imaging revealed diffuse white matter hyperintensities consistent with vasogenic edema. Autopsy revealed only widespread cerebral edema. Early recognition and persistent, aggressive treatment will be required to avoid this fatal and rare manifestation of neuropsychiatric lupus.     

Neuroblastoma survival and death: an in vitro model of hypoxia and metabolic stress

Heterogeneous oxygen tension and access to metabolites in solid tumors may produce variability in response to adjuvant therapy. To better understand these microenvironmental features, we examined survival and proliferation of neuroblastoma (NB) cells in an in vitro model of hypoxia and metabolite deprivation. Human NB cells (SH-SY5Y) were subjected to a "self-generated" diffusion gradient of nutrient and oxygen deprivation in a modified in vitro "sandwich model." In this model, the extent of both hypoxia and metabolite deprivation were individually altered, and the effects of each were studied. Cellular proliferation was confirmed by proliferating cell nuclear antigen (PCNA) immunocytochemistry and morphology and hypoxia by vascular endothelial growth factor (VEGF) and pimonidazole immunocytochemistry. We examined apoptotic cell death using TUNEL analysis, assaying for plasma membrane transfer of phosphotidylserine and the presence of the anti-apoptotic protein Bcl-2 using immunocytochemistry. As predicted, cellular survival diminished with increasing duration and severity of hypoxia and metabolite deprivation; oxygen deprivation was determined to be the more important contributory factor to early survival and proliferation. PCNA immunocytochemistry confirmed decreasing fractions of proliferating cells as a function of distance from oxygen and metabolites. VEGF and Bcl-2 immunoreactivity increased with prolonged exposure and increased extent of oxygen/metabolite deprivation. TUNEL analysis and phosphotidylserine transfer demonstrated cellular death of hypoxic and metabolite-deprived NB cells in a manner consistent with a mitochondrial apoptotic pathway. This in vitro model demonstrates that increasing the severity of hypoxia and metabolite deprivation results in diminished proliferation and greater apoptotic death, observations analogous to that of clinical NB tumors.     

The MELD score may help to determine optimum time for liver transplantation

BACKGROUND: The model for end-stage liver disease (MELD) score is a good predictor of mortality on the waiting list and short-term survival post liver transplantation. Aim: Our aim was to determine if there is a pretransplant MELD score beyond which liver transplantation is prohibitive. PATIENTS AND METHODS: Forty-six adult patients underwent primary liver transplantation from January 1996 to December 2002. Patients followed to the most recent visit or death underwent survival analysis using Cox regression and Kaplan Meier methods. RESULTS: There was a significant correlation between the pretransplant MELD score and survival at 6 months posttransplant (P=.037 95% CI: 1.004-1.13). Patients with pretransplant MELD score greater than or equal to 32 showed significantly greater mortality compared with those less than 32 (HR 9.18, 95%CI=1.16-72.44). CONCLUSION: Pretransplant MELD may help to determine the optimum time for liver transplantation.     

Persistent thrombocytopenia in liver transplant patients

INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period after a liver transplant is not uncommon. However, there are few studies on persistent thrombocytopenia during the longer follow up period of patients after liver transplantation. We examined the prevalence of and contributing factors to persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We analyzed adult patients followed for at least 1 year posttransplant with full blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35 patients of mean age at transplant of 50 years and showed a mean follow-up of about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of 54% and at 3 years of 25%. Factors that were associated with persistent thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis only the latter represented independent factors for persistent thrombocytopenia at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent thrombocytopenia improved over time posttransplant; no bleeding problem was observed among the affected cases.     

Renal impairment and diabetes mellitus after liver transplant

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.     

Widespread occurrence of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene haplotype SVMNT in P. falciparum malaria in India

The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) and the P. falciparum multidrug resistance 1 (Pfmdr1) mutation (N86Y) were analyzed as markers of chloroquine resistance in the DNAs of 73 blood samples from patients with P. falciparum malaria in India. Seventy of the 73 DNAs had the Pfcrt K76T mutation. Of these, 66 had the SVMNT haplotype and four had CVIET, the African/Southeast Asian haplotype. Only 20 of 69 DNAs had the Pfmdr1 N86Y mutation. It is surprising that the Pfcrt haplotype in India is predominantly SVMNT, rather than that seen in Southeast Asia. The widespread prevalence of the Pfcrt K76T mutation is a cause for concern.