A. Verbist

Tumor type and vascularity: Important variables in infusional brachytherapy with colloidal 32P

PURPOSE This study investigated the role of histologic tumor characteristics, in comparison with a normal tissue, and of tumor vascularization on the uptake and retention of colloidal 32P used in infusional brachytherapy of solid cancers. The cytotoxicity of colloidal 32P was also evaluated for two tumors of different radiosensitivity, a melanoma, and a squamous cell carcinoma. METHODS AND MATERIALS An in vitro analysis of colloidal 32P uptake was carried out on a human melanoma cell line, HBL, a human squamous cell carcinoma, SCC1, and normal fibroblasts, F-NBB. Tumor retention of colloidal 32P was studied in vivo for the HBL and the SCC1 tumors implanted subcutaneously in nude mice. Tumor vascular density was determined by microscopic study of Massons trichrome slides of HBL and SCC1 tumors of about 1 cm diameter. RESULTS In vitro studies showed that the time required for maximal cell uptake of colloidal 32P was only 10-20 min for the SCC1 and HBL tumors, while it took at least 60 min for the fibroblasts. After intratumoral injection of macroaggregated albumin (MAA), followed by 50 microCi of colloidal 32P, Bremsstrahlung imaging performed at 6 and 24 h showed that the activity remained in the HBL tumor while some of the radiocolloids leaked from the SCC1 tumor and was trapped in the reticuloendothelial system of the liver. Organ activity counting confirmed this finding: 32P activity was three to four times higher in the HBL than in the SCC1 tumor, whereas the activity in the liver, insignificant in the HBL mice (less than 0.1 microCi/g), was as high as 24 microCi/g in the SCC1 mice. This phenomenon may be explained by the difference in tumor vascular density, estimated for the HBL to be about four times less than that of the SCC1 tumor (5.7 vs. 21.4 blood vessels per mm2 for the HBL and the SCC1 tumors, respectively). CONCLUSION Intratumoral infusion of colloidal 32P may be a useful complement of radiation therapy in the treatment of nonresectable but accessible solid tumors. Tumor vascularization must be taken into account for a successful vascular blockade by MAA prior to the infusion of colloidal 32P.

Action of vasodilators on regional cerebral blood flow in subacute or chronic cerebral ischemia.

Regional cerebral blood flow (bicompartmental and stochastic method) was measured in a series of 20 patients with unilateral brain softening. Measurements were repeated during the administration of a vasodilator. A detrimental effect on the perfusion of the diseased area was observed in the majority of cases. It has been shown that the chances for a vasodilator to decrease the perfusion in the diseased area were greater when the angiogram showed obstruction of an intracranial artery.

Which diphosphonate for routine bone scintigraphy (MDP, HDP or DPD)?

Of 790 patients, 772 with proven cancerous disease have been studied without any selection using either MDP (three different kits), HDP (two types) or DPD. The groups were identical in age distribution, male/female ratio, body weight and verified percentage metastatic involvement. Technical conditions (Mo/Tc-generator used, dilution volume, total activity of the final product per vial, preparation/injection and injection/examination delays) were identical. Analogous scintigrams according to qualitative criteria (image quality, bone delineation, soft tissue fixation, metastatic/normal tissue contrast, aspecific uptake by non-target organs) and superior to MDP. Quantitative data were quite similar for all types of diphosphonates spine; metastatic/normal bone fixation ratio, bone/soft tissue ratio) have been evaluated. The results obtained showed that there was no criterion to demonstrate that HDP or DPD would be superior to MDP. Quantitative data were quite similar for all types of diphosphonates studied. Two out of the three MDPs were slightly superior to the other products with regard to detectability of metastatic lesions. Our results show, that in non-selected clinical routine work for bone scintigraphy HDP and DPD do not present any decisive qualitative or quantitative advantage in comparison to MDP.

Effect of 1% Enflurane (Ethrane) Anesthesia on Cerebral Blood Flow and Metabolism in Neurosurgical Patients during Normo- and Hyperventilation

We have measured the CBF in ten neurosurgical patients. A first measurment was made during anesthesia with nitrous oxide 70% and a second with nitrous oxide 70% + 1% enflurane, both at a PaCO2 of 40 Torr. A third measurement was performed also with nitrous oxide + 1% enflurane, but at a PaCO2 of 30 Torr. We used the method of intracarotid 133Xe injection, with a gammacamera recording. In order to avoid any decrease of cerebral perfusion pressure, which might influence the CBF, an infusion of phenylephrine was used, if needed. At a constant PaCO2 of 40 Torr, there was no statistically significant difference in CBF with nitrous oxide + 1% enflurane compared to nitrous oxide alone. No change in cerebral vascular resistance was observed. When PaCO2 was lowered to 30 Torr, under 70% nitrous oxide + 1% enflurane, there was a 43% decrease in CBF (from a mean of 42 ml/100 G/min. to a mean of 24 ml/100 g/min.). Cerebral vascular resistance had an increase of 79%. In some instances, the decrease in CBF reached values around 20 ml/100 g/min. and in one case, even less. That level is generally considered to be the lowest acceptable limit in the conscious man, though not necessarily in the anesthetised one. Under hypocapnia, the cerebral arterio-venous oxygen difference increased, but the CMRO2 did not change. There were little differences in lactate and pyruvate cerebral metabolic rates, all values remaining within normal ranges. In conclusion, we believe that enflurane is a favorable anesthetic agent for neurosurgical operations at the concentration of 1%, CMRO2 is reduced, there is no significant effect on cerebral blood vessels, CBF and CVR do not change. However, a complementary use of hypocapnia may reduce CBF to dangerously low levels, if at the start, it shows already a pathological decrease and if hyperventilation is applied at a marked degree.

THE ACTION OF ENFLURANE (ETHRANE) ON CEREBRAL BLOOD FLOW

Cerebral blood flow in the grey matter was measured by the 133Xenon method in 5 patients suffering from vascular brain lesion. A first measurement was performed under N 2O fentanyl anesthesia and a second under N 2O enflurane 1% anesthesia. For both tests the subjects were maintained under stable respiratory conditions and normocapnia by artificial ventilation. Enflurane 1% caused a reduction of cerebral blood flow in all 5 patients. The decrease varied between 5 and 23%, with a mean of 12%. The decrease of cerebral blood flow under enflurane is a favorable effect for its use in neurosurgery.