Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome.

Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.

Comparison of sequence analysis and INNO-LiPA HBV DR line probe assay in patients with chronic hepatitis B.

The aim of this study was to compare direct sequence analysis of partial HBV pol gene and Inno-LiPA HBV DR in serum samples of 120 chronic hepatitis B patients sent to the Clinical Microbiology Laboratory of Ege University Hospital because of lamivudine resistance. Sequence analysis was performed on ABI Prism 310 Genetic Analyzer. Comparison of Inno-LiPA and sequence results obtained by double-blind evaluation showed full agreement (both at rt180 and rt204) in 58.8% of samples. Visually rechecking of the electropherograms increased this rate to 68.3% Codon based rates are 81.7% and 75.8% at rt180 and rt204 respectively. LiPA detected variants in additional 12 (10%) samples, but missed one variant sample (both rt180 and rt204) and one sample was indeterminate due to poor probe binding. LiPA allows determination of mixed variants and seems to be more sensitive and simple for routine testing even though sequence analysis is still the gold standard for detecting new variants.

Outcome of pediatric liver transplant recipients in Turkey: single center experience.

To summarize the evolution of the pediatric liver transplant program in a developing country. Between April 1997, and September 2003, 32 cadaveric (CD) and 35 living donor (LD) liver transplantations were performed on 61 children (median age 3.8 yr, range 0.5-16) at Ege University Organ Transplantation and Research Center. The patient's charts were reviewed retrospectively. The outcome of patient and graft survival was analyzed and the incidence of graft loss, complications and rejections was calculated. Indications for liver transplantation were metabolic liver disease (n = 17), biliary atresia (n = 14), viral hepatitis (n = 4), autoimmune hepatitis (n = 6), cryptogenic cirrhosis (n = 11), fulminant liver failure (n = 5) and others (n = 5). Seven of 61 children with chronic liver disease had hepatocellular carcinoma concomitantly. Median pediatric end-stage liver disease score was 23 (range 1-54). Seven children (11.4%) were UNOS status I, 44 (72%) were UNOS status II and 10 (16.6%) were UNOS status III. The median follow-up of the study population was 3.6 yr (range 0.5-6). Actuarial patient survival rates at 1, 2, 3 and 4 yr were 86, 86, 71.3 and 65% in the CD group vs. 80, 76, 67 and 67% in the LR group, respectively (p = NS). Patients listed as UNOS status 1 had lower survival rates than patients listed as UNOS status 2 and 3 (p < 0.05). The mortality rate was 26.2%. Graft survival rates were 81, 81, 75 and 64% at 1, 2, 3 and 4-yr respectively. Six patients (9%) underwent retransplantation. The main complications were infections (64.7%) and surgical complications (43.2%) (including biliary complication, vascular problems, postoperative bleeding, small for size and large for size). The incidence of acute cellular rejection was 39.3%, whereas chronic rejection was 7.4%. The result of liver transplantation in Turkish children was slightly inferior to those reported for North American and European children. However, an important characteristic of these patients that distinguishes them from Europe and North America is that most were UNOS status IIa and UNOS status I (44%). Despite technical and medical progress, infectious and biliary problems have continued to be an important cause of mortality in these patients.

Transient fetal myelosuppressive effect of D-penicillamine when used in pregnancy.

Normal fertility is sustained by progress in the medical therapy of Wilson's disease; however, pregnancy complications are encountered more frequently. The mother we present is a Wilson's disease patient who had been compliant with D-penicillamine for the preceding 13 years. She was admitted with unplanned pregnancy at the 16th gestational week. The dose of D-penicillamine could be reduced to 600 mg/d related to the underlying disease. Pregnancy ended with premature labor and delivery at the 29-30th weeks. The baby experienced type I respiratory distress and was treated by surfactant and mechanical ventilation. Neutropenia and leucopenia were documented at 6th postnatal hours. The baby showed neutropenia and leucopenia for 5 days and resolving without any further therapy. Intrauterine D-penicillamine was suspected to cause transient neonatal myelosuppression.

Association between anti-endomysial antibody and total intestinal villous atrophy in children with coeliac disease.

BACKGROUND: There is growing evidence to suggest that detection of anti-gliadin antibody (AGA) and anti-endomysial antibody (EmA) can serve as sensitive markers of the degree of histological abnormalities in patients with coeliac disease. AIM: To evaluate the association between the presence of AGA and EmA and villous atrophy in intestinal biopsies of children with suspected coeliac disease. SETTINGS AND DESIGN: Intestinal samples of 46 children with failure to thrive, chronic diarrhoea, malabsorption and short stature with either AGA and/or EmA positivity were evaluated, retrospectively. The diagnosis of coeliac disease was based on ESPGHAN criteria. METHODS AND MATERIAL: Patients with total villous atrophy who fulfilled the ESPGHAN criteria for the diagnosis of coeliac disease were diagnosed to have coeliac disease. Nine patients without villous atrophy were taken as negative controls for this study. AGA-IgA was measured both by immunoflourescence (IF) and ELISA and EmA-IgA by IF while patients were on normal diet. Relationship between autoantibody positivity and intestinal total villous atrophy was evaluated. RESULTS: Overall positivity for AGA IgA was 85% (39/46) by IF+ELISA and EmA positivity was 85% (39/46) by IF within the study group. Histological examination revealed total villous atrophy with lymphocyte infiltration and crypt hyperplasia in 37 (80%) patients. AGA IgA was positive in 14 (38%) and 31 (84%) of these children by ELISA and IF, respectively. EmA positivity was detected in 35/37 (95%) cases with atrophy and 4/9 (44%) without atrophy (p=0.002). Thirty out of 37 (81%) patients with villous atrophy had both AGA IgA (IF) and EmA positivity (p=0.186). All of the sixteen patients that had both positive AGA IgA (ELISA+IF) and EmA had total villous atrophy (p=0.037). CONCLUSION: A significant association between total villous atrophy and EmA positivity has been documented in this study.

Immune status and autoantibody formation in children with chronic hepatitis B infection.

BACKGROUND: The hepatitis B virus (HBV) causes a wide spectrum of disease which ranges from acute hepatitis to liver cirrhosis. Patients who fail to mount a vigorous immune response in acute HBV develop chronic infection. Therefore, the aim of the study was to determine the cellular and humoral immune parameters of the patients with chronic HBV and to evaluate the prevalence of autoantibodies before the beginning of immunomodulator and antiviral therapy. METHODS: In this comparative study, serum immunoglobulins, IgG subclasses, secretory IgA, serum complement components, lymphocyte subsets and CD11a, CD18, CD54 molecules on lymphocytes were determined in 44 hospitalized patients of chronic HBV infection and 20 cases of healthy control subjects. RESULTS: Significant increase in IgG and significant decrease in the complement C4 were observed. The mean percentage of CD3+ lymphocytes, reflecting the percentage of total T cells was significantly higher in the patient group due to the increase of CD8+ lymphocytes. The mean percentage of CD19+ B lymphocytes was lower in the patient group secondary to the increase of their total T cells. No significant difference was found in cell surface adhesion molecules between patient and control groups. The percentage of antinuclear antibody positivity was 18.2%. CONCLUSIONS: Our data show that ANA formation is part of the natural course of chronic HBV infection and this value may reflect the tendency to autoimmune diseases and the importance of clinical follow-up. The abnormalities observed in immunological parameters may reflect the role of the cellular and humoral immune system in pathogenesis.

Comparison of tropisetron and granisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy.

Tropisetron and granisetron are selective serotonin (5-HT3) antagonists that have been proven effective in the prevention of nausea and vomiting in adults and children receiving cancer chemotherapy. This prospective, randomised study was designed to compare the efficacy of the two agents in the prevention of vomiting and nausea in children receiving highly emetogenic chemotherapy for various malignancies. A total of 51 children (mean age: 7.7 +/- 4.8 year) were studied in 133 chemotherapy cycles. In 66 chemotherapy cycles, the children received tropisetron as an antiemetic agent in a dose of 0.2 mg/kg/24 h intravenously and, in 67 cycles, they received granisetron 40 micrograms/kg/24 h intravenously before cytotoxic drug administration during the days they received chemotherapy. The response per 24 h of chemotherapy was defined as complete (no nausea and vomiting), partial (1-4 events of vomiting and/or nausea), and failure (more than 4 events of vomiting and/or nausea). Efficacy of antiemetic therapy was evaluated as acute (Day 1) and overall was based on the worst day during the chemotherapy. Complete control of acute vomiting was achieved in 74% of tropisetron and 88% of granisetron patients (P = 0.04), and complete control of acute nausea in 56% and 82% respectively (p = 0.002). Overall response by means of complete control of both vomiting and nausea during the whole therapy period was 29% of tropisetron group and 55% of granisetron group (p = 0.007). The statistical analysis (depending on the emetogenicity of the chemotherapy cycles) showed increased efficacy of granisetron in highly (grade 3) emetogenic chemotherapy cycles (p = 0.002), whereas there was no difference in the very highly emetogenic cycles (p = 0.7). Also, granisetron was found to be more effective than tropisetron, especially in patients heavier than 25 kg (p = 0.02). The adverse reactions were few and mild. There were no differences in the tolerability of the two antiemetic therapy modalities. In conclusion, granisetron was found to be more effective than tropisetron in controlling nausea and vomiting in children receiving highly emetogenic chemotherapy. This increased antiemetic efficacy of ganisetron might have been related to maximal dose differences according to body weight.

Inflammatory myofibroblastic tumor of small bowel wall in childhood: Report of a case and a review of the literature.

Benign intestinal tumors are rare in children, however we describe an inflammatory myofibroblastic tumor (IMT) of the jejunum in a 2-year-old girl who presented with an intestinal obstruction. During laparotomy, an annular mass around the jejunum was resected, from which a histological diagnosis of IMT was made. A review of the literature for this rare entity emphasizes the importance of histological confirmation of its benign nature. Because of the risk of local recurrence, IMT cases should have a long-term follow up.