Endoscopic insertion of biliary stents is the preferred method of palliation for inoperable malignant biliary obstruction; however, migration and clogging are frequent problems with conventional endoprostheses. We sought to determine if expandable metal stents offer improved palliation compared to conventional stents. Sixty-two patients with common bile duct lesions were randomized to receive polyethylene or metal stents. Stents were placed endoscopically or by the combined percutaneous-endoscopic route. Early results (< 1 month) were similar in both groups. Long-term follow-up (n = 28 polyethylene, median: 5 months; n = 27 metal, median: 5 months) showed a higher stent failure rate in the polyethylene (n = 12; 43%) compared to the metal group (n = 6; 22%). The incidence of cholangitis was significantly higher (p < 0.05) in the polyethylene (n = 10; 36%) compared to the metal group (n = 4; 15%). Life-table analysis showed a significantly reduced incidence of stent failure (p = 0.0035) in the metal stent compared to the polyethylene group. The total duration of hospital stay for treatment of stent related problems was significantly higher in the polyethylene (11.8 +/- 3 days) compared to the metal group (4 +/- 1.9 days; p = 0.02). The costs for retreatment because of stent failure were significantly higher in the plastic (DM 5900 +/- 1516) compared to the metal group (DM 2070 +/- 977). As a result, the overall costs (treatment of stent related complications & stents) were higher in the polyethylene group (DM 6000 +/- 1500).(ABSTRACT TRUNCATED AT 250 WORDS)

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1. The interrelationship between the two carbamoyl phosphate pools in intact hepatocytes and intact liver was studied with respect to de novo pyrimidine synthesis by use of selective inhibitors of the mitochondrial and the cytosolic carbamoyl-phosphate synthetase.2. Inhibition of mitochondrial carbamoyl phosphate synthesis by 4-pentenoate was without effect on galactosamine-stimulated pyrimidine synthesis. Conditions favouring mitochondrial carbamoyl phosphate accumulation, like excess ammonium ions or L-norvaline, led to an increase in pyrimidine synthesis bypassing the feedback inhibition of cytosolic carbamoyl-phosphate synthetase by UTP.3. A stimulation of pyrimidine synthesis was not observed when the carbamoyl phosphate accumulation was due to aspartate deficiency in the presence of aminooxyacetate. The full response of pyrimidine synthesis to excess ammonium ions was restored, even in the presence of aminooxyacetate, when aspartate was substituted. This is explained by an inhibition of aspartate carbamoyltransferase flux [in view of the K,,, (aspartate = 0.7 mmol/l) of this enzyme] resulting from a 90% decrease in aspartate tissue levels.4. Acivicin, the inhibitor of cytosolic carbamoyl-phosphate synthetase, completely abolished the galactosamine-induced stimulation of pyrimidine synthesis, but was without effect on the stimulation of pyrimidine synthesis by ammonium ions and L-norvaline.5. It is concluded that experimental changes in mitochondrial carbamoyl phosphate content exert effects on de novo pyrimidine synthesis; however, it is considered unlikely that relevant amounts of mitochondrial carbamoyl phosphate are used for pyrimidine synthesis under physiological conditions. In addition the data point to a potential regulatory role of aspartate in hepatic pyrimidine synthesis.In the liver of mammals carbamoyl phosphate, as common substrate of the synthesis of arginine and urea and the de novo pyrimidine synthesis, is synthesized by two different enzymes. The mitochondrial carbamoyl-phosphate synthetase (CPS I) supplies carbamoyl phosphate for the synthesis of urea [I -31. It requires ammonium ions as substrate and N-acetyl-L-glutamate as allosteric activator [I, 41. At physiological ammonium ion concentrations the CPS I flux is rate-limiting for urea synthesis [5]. The much less active cytoplasmic glutaminedependent carbamoyl-phosphate synthetase (CPS 11) provides carbamoyl phosphate for the de novo synthesis of pyrimidines [l, 6, 71. This enzyme is the site of feedback inhibition by UTP regulating de novo pyrimidine synthesis [I, 81. Furthermore, it is activated by physiological concentraCorrespondence to 3 .