Gastrointestinal stromal tumour presenting with severe bleeding: a review of the molecular biology.

Gastrointestinal stromal tumours (GIST) are rare in children. A 7-year-old boy presented acutely with a severe upper gastrointestinal bleed and was found following angiography to have such a tumour in the duodenum, which was resected at laparotomy. The presence of CD 117 positive immunostaining was a confirmatory diagnostic marker. The prognosis and underlying molecular biology of the tumour is discussed. Understanding of the molecular pathogenesis has given rise to promising new therapies.

Outcome and complications after resection of hepatoblastoma.

PURPOSE: The aim of this study was to review the outcome and complications after resection of hepatoblastoma treated over 2 decades in our institution. METHODS: Clinical, radiologic, and pathologic data were reviewed retrospectively, focusing on the outcome and complications. RESULTS: Between January 1978 and December 2002, 56 children were treated for hepatoblastoma. The age range was 0.08 to 8.74 years (median, 1 year). The right lobe was involved in 48%, the left lobe in 22%, and in 29% the main bulk of the tumour was centrally located. Surgical procedures included the following: hemihepatectomy in 62%, trisegmentectomy in 18%, extended hemihepatectomy in 16%, and liver transplantation and laparotomy in one patient each. Intraoperative complications occurred in 5(9%)--rupture of the tumour (1), haemorrhage from the contralateral lobe (1), a defect in the left hepatic duct (1), cardiac arrest from tumour embolus (1), and bleeding from the inferior vena cava (1). The mean blood loss was 280 mL (50 to 2,000 mL). Postoperative complications occurred in 12 patients (22%) including subphrenic abscess (3), adhesion obstruction (2), ischaemic stenosis of the bile duct (1), abdominal wound dehiscence (1), pyloric obstruction (1), and pleural effusion (2). Fifteen patients died, 14 as a result of tumour recurrence (mortality rate, 27%).

Uptake of lipiodol-cytotoxics conjugates by hepatocellular carcinoma cells.

PURPOSE: The aim of this study was to quantify the uptake of anthracyclic cytotoxic drugs by hepatocellular carcinoma cells and the effect of Lipiodol, an iodinated poppy seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatocellular carcinoma (HCC) cells. METHODS: Monolayers of hepatocellular carcinoma cell line (HepG2) and a normal human hepatocyte cell line were exposed to 10 microg/mL doxorubicin or epirubicin with or without 2% lipiodol for 1 to 72 hours. The fluorescence intensity in the cytospin and fixed cell were measured using confocal laser scanning microscope. RESULTS: The uptake of both doxorubicin and epirubicin by the HCC cells was mainly cytoplasmic. The mean fluorescence intensity at 24 hours of lipiodol-doxorubicin-treated cells was increased to 80.7 pixel units, whereas doxorubicin-treated cells intensity was 47.9 pixel units (P <.05). Lipiodol did not have any effect on the uptake of epirubicin. Clonogenic assay confirmed a significant sensitivity difference between doxorubicin and epirubicin-treated hepatocellular carcinoma cell lines. CONCLUSIONS: Lipiodol has a selective effect on the uptake of certain cytotoxic agents. Lipiodol-doxorubicin-targeted treatment of hepatocellular carcinoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo.

Uptake of Lipiodol--cytotoxic conjugates by hepatoblastoma cells.

BACKGROUND: Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture. METHODS: Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy. RESULTS: Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells. CONCLUSION: Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.

In-vitro uptake of radioactive lipiodol I-131 and I-125 by hepatoblastoma: implications for targeted radiotherapy.

Lipiodol, a stable iodine addition product of fatty ethyl esters derived from poppyseed oil, has been used as a vehicle for targeted cytotoxic or radiotherapeutic treatment in adults with unresectable hepatocellular carcinoma and in a few children with advanced hepatoblastoma (HB). Prolonged retention of lipiodol by the cancer cells might enable more effective targeted therapy to advanced, multifocal, or metastatic HB. To investigate the uptake and cytotoxic efficacy of beta and Auger electron-emitting radioconjugates on HB cells, monolayers of HB (C3a, Hep Tow1) and normal human hepatocyte cell lines were exposed to lipiodol131 (L131), lipiodol125 (L125), or a cocktail of both isotopes. Uptake of radioactivity was assessed autoradiographically using phosphoimages and the cytotoxicity assessed by trypan blue exclusion and clonogenic assay. The uptake of the different radioconjugates was identical in both HB cell lines. The "cocktail" of both radioactive lipiodols caused the greatest cytotoxicity to HB C3a, and HepTow1. L125 alone had a similar level of uptake and cytotoxicity as L131. Radioactive iodine alone did not show any cytotoxicity on any of the liver cell lines in culture for up to 72 h. These experimental results provide support for a clinical strategy of combinations ("cocktails") of radioconjugates in targeted radiotherapy in patients with HB.

Laparoscopic orchidopexy: one-stage alternative for non-palpable testes.

Laparoscopy was utilised in the evaluation of 24 non-palpable undescended testes in 19 children. The procedure was accurate in all patients while ultrasound (US) and magnetic resonance imaging (MRI) failed to localise the testes in most cases. At the same time laparoscopic orchidopexy was performed on 15 testes (62.5%). The remaining testes were either absent or atrophic, in which case they were excised. There were no complications from these procedures and the hospital stay was short. Paediatric laparoscopy is safe and effective in the definitive management of non-palpable undescended testes.

Management of the colonised shunt.

A system of management is described for colonised hydrocephalus shunts. If organisms have reached the lateral ventricles as well as the valve chamber, the shunt must be removed and the ventricles drained externally with instillation of a suitable antibiotic until the fluid is sterile. If the ventricular fluid is not infected the shunt can safely be replaced at the same operation, using a site on the opposite side of the head. The operation has been performed 12 times without reinfection.