Hepatic intra-arterial lipiodol ultrasound guided biopsy in the management of hepatocellular carcinoma.

One hundred and fifty-one consecutive new patients with suspected hepatocellular carcinoma (HCC) were investigated from 1989 to 1990. Ultrasound showed the tumours to be inoperable in 111 patients. Selective hepatic angiography revealed 17 more patients with inoperable HCC. Hepatic intra-arterial lipiodol (HIAL) was injected in the remaining 23 patients. In 16 of them, a clinical decision could be reached basing on the radiological findings. Hepatic intra-arterial lipiodol ultrasound (HIAL/USG) guided biopsy was done in seven patients with suspicious lesions. Histology obtained with this method revealed hyperplastic cirrhotic nodules in four patients (two with suspected HCC and two with suspected secondaries). In another two patients, the suspected lesions were confirmed to be malignant. In the last patient who had received chemotherapy for extensive HCC, HIAL/USG guided biopsy revealed necrotic tissue only. At laparotomy, diffuse infiltrative abnormality was found and repeated biopsy confirmed residual malignancy in the necrotic tumour. We conclude that when there is radiological uncertainty as to the nature and extent of the HCC, HIAL/USG guided biopsy can help the clinician to make important decisions.

Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.

Treatment of inoperable hepatocellular carcinoma by intra-arterial lipiodol and 4'-epidoxorubicin.

A total of 30 patients presenting with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial Lipiodol (5 ml) and 4'-epidoxorubicin (90 mg/m2) once every 4 weeks. The treatment results included no complete response, 2 partial responses, 6 cases of static disease and 19 cases of progressive disease. The median survival was 18.9 weeks. All patients had died by the time of this writing, with survival duration ranging from 4.1 to 87.3 weeks. Toxicities were minimal and included anaemia and alopecia. As compared with a historic control group that had received the same dose of intravenous 4'-epidoxorubicin, the treatment group showed similar response rates but developed fewer toxicities. There was no significant survival benefit over the control group. We concluded that although this form of treatment had comparable activity and produced fewer side effects, it provided no survival benefit over intravenous treatment. The slight prolongation of survival achieved in the treatment group as compared with the control arm might have been due to case selection.

A randomised cross-over trial comparing low-dose metoclopramide and chlorpromazine with high-dose metoclopramide in Chinese patients with advanced cancer receiving cisplatinum and 5-fluorouracil.

Nineteen Chinese patients receiving chemotherapy for advanced cancer were studied for chemotherapy-induced acute nausea and vomiting. The chemotherapy consisted of cisplatinum 100 mg/m2 i.v. infusion over 4 h on day 1 and 5-fluorouracil (5-FU) 1000 mg/m2 120-h continuous infusion from day 2 to day 6, repeated every 3 weeks. At the first course of chemotherapy the patients were randomized to receive either low-dose metoclopramide and chlorpromazine or high-dose metoclopramide, and then crossed over for the second course. In the high-dose metoclopramide group there was a suggestion of an earlier onset of emesis, with slightly more frequent retching and vomiting and less food consumed. However, the duration of emesis was shorter in the high-dose group. These differences were not statistically significant. There were no major side effects. Mild salutary drowsiness was noticed in patients receiving low-dose metoclopramide and chlorpromazine. This trial suggests that, in the dosage, route and schedule described, high-dose metoclopramide is no more effective than low-dose metoclopramide together with chlorpromazine in preventing cisplatinum-induced nausea and vomiting. The low-dose scheme is more economic and suitable for patients with advanced cancer.