Original Articles
Copyright ©The Author(s) 1999. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 1999; 5(6): 492-505
Published online Dec 15, 1999. doi: 10.3748/wjg.v5.i6.492
Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma
Lu Liu, Zao Jiang, Gao-Jun Teng, Ji-Zhi Song, Dong-Sheng Zhang, Qing-Ming Guo, Wen Fang, Shi-Cheng He, Jin-He Guo
Lu Liu, Zao Jiang, Gao-Jun Teng, Ji-Zhi Song, Dong-Sheng Zhang, Qing-Ming Guo, Wen Fang, Shi-Cheng He, Jin-He Guo, Experimental Center of Modern Medical Sciences, Nanjing Railway Medical College, Nanjing 210009, Jiangsu Province, China
Lu Liu, M.D. female, born in 1946-10-17 in Jinan, Shandong Province, Han nationality, graduated from Nanjing Railway Medical College in 1970 and is now an Associate Professor, majoring in nuclear medicine and having more than 50 papers published at home and abroad.
Author contributions: All authors contributed equally to the work.
Supported by the Science and Technology Commission of Jiangsu Province, No. BJ93077. Sponsored by Project No. 863 of National High-Tech Research and Development Program, No. 715-002-0200.
Correspondence to: LIU Lu, Experimental Center of Modern Medical Sciences, Nanjing Railway Medical College, Nanjing 210009, China. xue-c@263.net
Telephone: +86-25-3301508 Ext. 2708 Fax: +86-25-3426368
Received: July 14, 1999
Revised: August 16, 1999
Accepted: September 3, 1999
Published online: December 15, 1999

AIM: To study the therapeutical effectiveness, dosage range an d 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 w ere allocated into treatment group ( n = 38) and control group ( n = 14). In the former group different doses of 32P-GMS were injected into the tumor mass, while in the latter 31P-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 catheterizati on of hepatic artery, 32P-GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31P-GMS was infused to another 5 healthy domestic pigs. Two pigs infused with con trast 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 ultrastructur al histopath-ological changes in liver tissues taken from different sites were evaluated semiquan-titatively. III. One hundred and twenty-seven times of 32P-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 hepati c carcinoma. 32P-GMS ( n = 30), and group B, 32P-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 14d. 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 32P-GMS. II. The cumulative amount of 32P-GMS in the target tissue after trans-hepatic artery instillation attained more than 90% of the tot al dose administrated. Semiquantitative analysis of ultrastructral morphology in the experimental group showed no statistical difference between the nuclear abnormality ( nabn) and mitochondrial variability (Mvar) at week 1 or 2 , but revealed prominent difference ( χ2 = 6.70-9.68, P < 0.01, χ2 = 65.09-115.09, P < 0.001) as compared with those in the other groups. In the experimental group the nabn 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 3mos after treatment. In group C the collateral circulation was reestablished along the periphery of primary foci and the secondary foci appeared more frequently, and were required to undergo several courses of treatment. In group B, 4 cases of HCC were treated surgically as their mass decreased in size after 32P-GMS treatment. Resected specimens showed that the tumor was encapsulated by fibrotic tissue and most of the tumor cells necrosed. The 3-year survival rates were 43.3%-51.0% after A and B regimen treatment. In 14 cases of secondary HCC, the foci were well controled within one year after-treatment.

CONCLUSION: When the experimental model of implanted human liver cancer cells received 32P-GMS of 1830Gy-3660Gy, it produced excellent anticancer effect without any injury to the normal neighboring tissues and the prominent anticancer effect was shown within 3d after intratumoral injec tion. Intrahepatic arterial administration of 32P-GMS at the macrocosmic absorbed dosage less than 190 Gy/dose exerted reversible sub-lethal injury to domestic pig liver tissues. It took more than 8 weeks to repair the injured liver tissue and restore its function. 32P-GMS trans-hepatic artery embolization is an effective and safe regimen in treating hepatic carcinoma.

Keywords: liver neoplasms/therapy, phosphorus-32 glass microspheres ( 32P-GMS ), 31P-GMS, interventional therapy