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. 1996 Apr;73(8):961–965. doi: 10.1038/bjc.1996.188

Increasing hepatic arterial flow to hypovascular hepatic tumours using degradable starch microspheres.

D Chang 1, S A Jenkins 1, S J Grime 1, D M Nott 1, T Cooke 1
PMCID: PMC2075812  PMID: 8611432

Abstract

The effect of degradable starch microspheres (DSM) on the intrahepatic distribution of a low molecular weight marker, 99Tcm-labelled methylene diphosphonate (MDP), was studied in rats with hypovascular HSN liver tumours. MDP was injected regionally, via the hepatic artery, alone or co-administered with DSM, with or without subsequent occlusion of either the hepatic artery or the portal vein. Tumour vascularity was measured with 57Co-labelled microspheres. Co-injection with DSM immediately significantly increased hepatic retention of marker in both tumour (T) (median 22.40 (range 16.82-39.58)% injected dose) and normal liver (N) (9.08 (4.85-12.59) %ID) the greater effect seen in T (P < 0.01). After DSM degradation, very little MDP remained in N (0.61 (0.28-1.40) %ID) but there was significant retention in T (10.01 (6.73-20.28) %ID, P < 0.01). Clamping the hepatic artery had minimal effect on the retention of MDP when administered alone. Regional injection of 16.5 microM 57Co microspheres resulted in a N:T ratio of 2.25:1. Concomitant injection of the 40 microM DSM was 57Co microspheres reversed this ratio to 1:2. The results indicate that DSM selectively enhances the retention of MDP to a hypovascular hepatic tumour, not by causing intra-tumour stasis, but by directing a greater arterial flow to hypovascular areas in the liver.

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Selected References

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  1. Ackerman N. B., Lien W. M., Silverman N. A. The blood supply of experimental liver metastases. 3. The effects of acute ligation of the hepatic artery or portal vein. Surgery. 1972 Apr;71(4):636–641. [PubMed] [Google Scholar]
  2. Ackerman N. B. The blood supply of experimental liver metastases. IV. Changes in vascularity with increasing tumor growth. Surgery. 1974 Apr;75(4):589–596. [PubMed] [Google Scholar]
  3. Arfors K. E., Forsberg J. O., Larsson B., Lewis D. H., Rosengren B., Odman S. Temporary intestinal hypoxia induced by degradable microspheres. Nature. 1976 Aug 5;262(5568):500–501. doi: 10.1038/262500a0. [DOI] [PubMed] [Google Scholar]
  4. Buckberg G. D., Luck J. C., Payne D. B., Hoffman J. I., Archie J. P., Fixler D. E. Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol. 1971 Oct;31(4):598–604. doi: 10.1152/jappl.1971.31.4.598. [DOI] [PubMed] [Google Scholar]
  5. Burton M. A., Gray B. N., Klemp P. F., Kelleher D. K., Hardy N. Selective internal radiation therapy: distribution of radiation in the liver. Eur J Cancer Clin Oncol. 1989 Oct;25(10):1487–1491. doi: 10.1016/0277-5379(89)90109-0. [DOI] [PubMed] [Google Scholar]
  6. Civalleri D., Rollandi G., Simoni G., Mallarini G., Repetto M., Bonalumi U. Redistribution of arterial blood flow in metastases-bearing livers after infusion of degradable starch microspheres. Acta Chir Scand. 1985;151(7):613–617. [PubMed] [Google Scholar]
  7. Ensminger W. D., Gyves J. W. Clinical pharmacology of hepatic arterial chemotherapy. Semin Oncol. 1983 Jun;10(2):176–182. [PubMed] [Google Scholar]
  8. FISHER E. R., TURNBULL R. B., Jr The cytologic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma. Surg Gynecol Obstet. 1955 Jan;100(1):102–108. [PubMed] [Google Scholar]
  9. Flowerdew A. D., Richards H. K., Taylor I. Temporary blood flow stasis with degradable starch microspheres (DSM) for liver metastases in a rat model. Gut. 1987 Oct;28(10):1201–1207. doi: 10.1136/gut.28.10.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greenway C. V., Oshiro G. Comparison of the effects of hepatic nerve stimulation on arterial flow, distribution of arterial and portal flows and blood content in the livers of anaesthetized cats and dogs. J Physiol. 1972 Dec;227(2):487–501. doi: 10.1113/jphysiol.1972.sp010044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HEALEY J. E., Jr VASCULAR PATTERNS IN HUMAN METASTATIC LIVER TUMORS. Surg Gynecol Obstet. 1965 Jun;120:1187–1193. [PubMed] [Google Scholar]
  12. Kim D. K., Watson R. C., Pahnke L. D., Fortner J. G. Tumor vascularity as a prognostic factor for hepatic tumors. Ann Surg. 1977 Jan;185(1):31–34. doi: 10.1097/00000658-197701000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lautt W. W. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol. 1985 Nov;249(5 Pt 1):G549–G556. doi: 10.1152/ajpgi.1985.249.5.G549. [DOI] [PubMed] [Google Scholar]
  14. Lin G., Lunderquist A., Hägerstrand I., Boijsen E. Postmortem examination of the blood supply and vascular pattern of small liver metastases in man. Surgery. 1984 Sep;96(3):517–526. [PubMed] [Google Scholar]
  15. Lindell B., Aronsen K. F., Nosslin B., Rothman U. Studies in pharmacokinetics and tolerance of substances temporarily retained in the liver by microsphere embolization. Ann Surg. 1978 Jan;187(1):95–99. doi: 10.1097/00000658-197801000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lorelius L. E., Benedetto A. R., Blumhardt R., Gaskill H. V., 3rd, Lancaster J. L., Stridbeck H. Enhanced drug retention in VX2 tumors by use of degradable starch microspheres. Invest Radiol. 1984 May-Jun;19(3):212–215. [PubMed] [Google Scholar]
  17. McCuskey R. S. A dynamic and static study of hepatic arterioles and hepatic sphincters. Am J Anat. 1966 Nov;119(3):455–477. doi: 10.1002/aja.1001190307. [DOI] [PubMed] [Google Scholar]
  18. Niederhuber J. E., Ensminger W., Gyves J., Thrall J., Walker S., Cozzi E. Regional chemotherapy of colorectal cancer metastatic to the liver. Cancer. 1984 Mar 15;53(6):1336–1343. doi: 10.1002/1097-0142(19840315)53:6<1336::aid-cncr2820530620>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  19. Nott D. M., Yates J., Grime J. S., Maltby P., O'Driscoll P. M., Baxter J. N., Jenkins S. A., Cooke T. G. Induced hepatic arterial blockade by degradable starch microspheres in the rat. Nucl Med Commun. 1987 Dec;8(12):1019–1024. doi: 10.1097/00006231-198712000-00011. [DOI] [PubMed] [Google Scholar]
  20. Rappaport A. M. The microcirculatory hepatic unit. Microvasc Res. 1973 Sep;6(2):212–228. doi: 10.1016/0026-2862(73)90021-6. [DOI] [PubMed] [Google Scholar]
  21. Schwartz S. I., Jones L. S., McCune C. S. Assessment of treatment of intrahepatic malignancies using chemotherapy via an implantable pump. Ann Surg. 1985 May;201(5):560–567. doi: 10.1097/00000658-198505000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sigurdson E. R., Ridge J. A., Daly J. M. Intra-arterial infusion of doxorubicin with degradable starch microspheres. Improvement of hepatic tumor drug uptake. Arch Surg. 1986 Nov;121(11):1277–1281. doi: 10.1001/archsurg.121.11.1277. [DOI] [PubMed] [Google Scholar]
  23. Teder H., Aronsen K. F., Björkman S., Lindell B., Ljungberg J. The influence of degradable starch microspheres on liver uptake of 5-fluorouracil after hepatic artery injection in the rat. J Pharm Pharmacol. 1986 Dec;38(12):939–941. doi: 10.1111/j.2042-7158.1986.tb03391.x. [DOI] [PubMed] [Google Scholar]
  24. Yipintsoi T., Dobbs W. A., Jr, Scanlon P. D., Knopp T. J., Bassingthwaighte J. B. Regional distribution of diffusible tracers and carbonized microspheres in the left ventricle of isolated dog hearts. Circ Res. 1973 Nov;33(5):573–587. doi: 10.1161/01.res.33.5.573. [DOI] [PMC free article] [PubMed] [Google Scholar]

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