Clinical and experimental study on regional administration of phosphorus32 glassmicrospheres in treating hepatic carcinoma

AIM To study the therapeutical effectiveness, dosage range and toxic adverse effects of domestic phosphorus 32 glass microsphere and evaluate its clinical significance. METHODS Ⅰ. Fifty two BALB/*!c tumor bearing male nude mice were allocated into treatment group( n =38) and control group( n =14). In the former group different doses of 32 P GMS were injected into the tumor mass, while in the latter 31 P GMS or no treatment was given. The experimental animals were sacrificed in batches, and then the tumors and their nearby tissues were examined by light and electron microscopy. Ⅱ. Through selective catheterization of hepatic artery, 32 P GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31 P GMS was infused to another 5 healthy domestic pigs. Two pigs infused with contrast medium served as whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 4, 8 and 16 respectively. The ultrastructural histopath ological changes in liver tissues taken from different sites were evaluated semiquan titatively. Ⅲ. One hundred and twenty seven times of 32 P GMS intrahepatic artery interventional therapies were performed on 93 patients with hepatic carcinoma, including 79 cases of primary hepatic carcinoma and 14 cases of secondary hepatic carcinoma. 32 P GMS ( n =30), and group B, 32 P GMS and half dose of trans hepatic artery embolization (TAE) ( n =49) , and 18 patients with HCC by TAE only as control group C. Fourteen patients with secondary hepatic carcinoma were treated in the same way as group B or C. RESULTS Ⅰ. Comparing with the control group, the treatment group of tumor bearing nude mice attained the tumor inhibition rates of 59 7%-93 7% ( F =579 62, P <0 01) at 14*!d . At an absorbed dose of 7320Gy, the tumor cells were completely destroyed. When the absorbed doses ranged from 1830Gy to 3660Gy, most of the tumor cells showed the evidences of injury or necrosis, but there appeared some well differentiated tumor cells and enhanced effect of the autoimmunocytes. At an absorbed dose of 366Gy or less, some tumor cells still remained active proliferative ability. The definite anticancer effect appeared as early as 3d after intratumoral injection of 32 P GMS. Ⅱ. The cumulative amount of 32 P GMS in the target tissue after trans hepatic artery instillation attained more than 90% of the total dose administrated. Semiquantitative analysis of ultrastructral morphology in the experimental group showed no statistical difference between the nuclear abnormality (N abn ) and mitochondrial variability (M var ) at week 1 or 2, but revealed prominent difference (χ 2=6 70-9 68, P <0 01 , χ 2=65 09-115 09, P <0 001 ) as compared with those in the other groups. In the experimental group the N abn in tissues showed no significant difference between week 8 and week 16. No apparent changes were found in the stomach, spleen, kidney and lung tissues of the experimental pigs. Ⅲ. The therapeutical results of HCC patients in group A were closely approximated to those of group C, no hematological toxic side effects were noted, and the systemic reaction was mild. In some patients 2*!mos - 3*!mos after treatment some secondary foci appeared around the periphery of the primary lesion. In general better effectiveness was obtained in patients with small lesion. After analyzing by RIDIT method, the therapeutic result in group B was significantly better than that in group C, and secondary foci around the original lesion were rarely seen at 3*!mos after treatment. In group C the collateral circulation was reestablished along the periphery of primary foci and the secondary foci appeared more frequently, and required to undergo several courses of treatment. In group B, 4 cases of HCC were treated surgically as their mass decreased in size after 32 P GMS treatment.

Effect of Phosphorus-32 Glass Microspheres on the Human Hepatocellular Carcinoma in Nude Mice

Objective To study anticancer effect and ultrastructural influence of phosphorus 32 glass microspheres( 32 P GMS) injected in the hepatocellular carcinoma in nude mice. MethodsThe ultrastructural changes of tumor in both the treatment group and control group were examined by transmission electron microscope. ResultsIn the treatment group,a large number of tumor cells were killed and the death rate of tumor cells was much higher(35%-70%). Ultrastructurally, severe nuclear damage was observed in the dead cells. The early characteristics of necrosis such as margination of heterochromatin were also found in some tumor cells. Besides,well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. The skin and muscle close to the tumor were normal. In the control group,the tumor consisted of poor differentiated tumor cells,in which there were only a few appototic cells(5%). ConclusionThe results suggest that the local administration of 32 P GMS produces obviously the anticancer effect.

Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs

Objective To evaluate the toxic response to intrahepatic arterial admin istration of radioactive phosphorus32 glass microspheres (32 P GMS) in domestic pigs Methods Through selective catheterization of hepatic artery,32P GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the thera peutic dose for human being, and31PGMS was infused to other 5 healthy domestic pigs Two pigs se rved as the whole course blank controls One pig from each group was surrendere d to euthanasia at week 1, 2, 4, 8 and 16, respectively, and liver biopsies were performed on the rest of pigs at the corresponding time points Liver tissues f r om different sites were taken for light and electron microscopy The ultrastruc t ural histopathological changes were evaluated semiquantitatively Results The accumulative amount of32PGMS in the target tissue attained more th an 90% of the total dose administrated Histologically, abnormal hepatocytes we re easily found at week 1 or 2 At week 4 they were less than at week 1 or 2, a n d endothelium of the sinuses were damaged prominently At week 8 they were scar cely seen, and liver tissue recovered gradually The histological features of l i ver tissue restored to normal at week 16 Semiquantitative analysis of ultrastr u ctural morphology in the experimental group showed no statistical difference ( P >050) between the nuclear abnormality (Nabn) and mitochrondri a l variability (Mvar) at week 1 or 2, but revealed prominent difference ( P <001, P <0001) as compared with those in other groups I n the experimental group the Nabn in tissues showed no significant differe nce ( P >020) between week 8 and week 16 Conclusion 32 PGMS internal irradiation at the dosag e equiva lent to human therapeutic dosage exerts reversible injury to domestic pig liver tissue, and it takes more than 8 weeks for the injured liver tissue to recover