Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1985 Mar;201(3):337–343. doi: 10.1097/00000658-198503000-00014

Isolation-perfusion of the liver with 5-fluorouracil.

W F Sindelar
PMCID: PMC1250676  PMID: 3977437

Abstract

Isolation-perfusion of the liver was performed in ten pigs using 5-fluorouracil administered in the perfusion circuit at doses of 100, 250, 500, and 1000 mg/kg body weight. Perfusion was performed for 60 minutes at normothermic (37 C) or hyperthermic (41 C) temperatures. One animal died shortly after perfusion. Incomplete isolation of the hepatic vasculature in two animals resulted in significant drug leakage into the systemic circulation with resulting hematologic toxicity. Perfusion with 5-fluorouracil at 1000 mg/kg produced hepatic necrosis. Perfusion with 5-fluorouracil at doses of 100, 250, or 500 mg/kg produced no hepatic toxicity except for transient elevations of hepatic enzymes and resulted in no systemic drug toxicity. Levels of 5-fluorouracil tolerated by the liver in the isolation-perfusion system were more than 1000-fold greater than the maximum drug levels achievable by routine systemic, intra-arterial, or intraperitoneal administration.

Full text

PDF
343

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AUSMAN R. K., AUST J. B. Isolated perfusion of the liver with HN2. Surg Forum. 1960;10:77–79. [PubMed] [Google Scholar]
  2. Boddie A. W., Jr, Booker L., Mullins J. D., Buckley C. J., McBride C. M. Hepatic hyperthermia by total isolation and regional perfusion in vivo. J Surg Res. 1979 Apr;26(4):447–457. doi: 10.1016/0022-4804(79)90033-7. [DOI] [PubMed] [Google Scholar]
  3. Ensminger W. D., Rosowsky A., Raso V., Levin D. C., Glode M., Come S., Steele G., Frei E., 3rd A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil. Cancer Res. 1978 Nov;38(11 Pt 1):3784–3792. [PubMed] [Google Scholar]
  4. HEALEY J. E., Jr, SMITH J. L., Jr, CLARK L., Jr, STEHLIN J. S., Jr, WHITE E. C. Hepatic tissue tolerance to thio-TEPA administered by the isolation-perfusion technique. J Surg Res. 1961 Jul;1:111–116. doi: 10.1016/s0022-4804(61)80006-1. [DOI] [PubMed] [Google Scholar]
  5. Hillcoat B. L., McCulloch P. B., Figueredo A. T., Ehsan M. H., Rosenfeld J. M. Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion. Br J Cancer. 1978 Dec;38(6):719–724. doi: 10.1038/bjc.1978.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. KESTENS P. J., FARRELLY J. A., MCDERMOTT W. V., Jr A technique of isolation and perfusion of the canine liver. J Surg Res. 1961 May;1:58–63. doi: 10.1016/s0022-4804(61)80023-1. [DOI] [PubMed] [Google Scholar]
  7. Krementz E. T., Carter R. D., Sutherland C. M., Hutton I. Chemotherapy of sarcomas of the limbs by regional perfusion. Ann Surg. 1977 May;185(5):555–564. doi: 10.1097/00000658-197705000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McBride C. M. Sarcomas of the limbs. Results of adjuvant chemotherapy using isolation perfusion. Arch Surg. 1974 Aug;109(2):304–308. doi: 10.1001/archsurg.1974.01360020164032. [DOI] [PubMed] [Google Scholar]
  9. Mulcare R. J., Solis A., Fortner J. G. Isolation and perfusion of the liver of cancer chemotherapy. J Surg Res. 1973 Aug;15(2):87–95. doi: 10.1016/0022-4804(73)90147-9. [DOI] [PubMed] [Google Scholar]
  10. Sindelar W. F. Method of isolation-perfusion of the liver in the pig. Am Surg. 1984 Oct;50(10):557–563. [PubMed] [Google Scholar]
  11. Skibba J. L., Almagro U. A., Condon R. E., Petroff R. J., Jr A technique for isolation perfusion of the canine liver with survival. J Surg Res. 1983 Feb;34(2):123–132. doi: 10.1016/0022-4804(83)90051-3. [DOI] [PubMed] [Google Scholar]
  12. Skibba J. L., Condon R. E. Hyperthermic isolation-perfusion in vivo of the canine liver. Cancer. 1983 Apr 1;51(7):1303–1309. doi: 10.1002/1097-0142(19830401)51:7<1303::aid-cncr2820510721>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  13. Speyer J. L., Collins J. M., Dedrick R. L., Brennan M. F., Buckpitt A. R., Londer H., DeVita V. T., Jr, Myers C. E. Phase I and pharmacological studies of 5-fluorouracil administered intraperitoneally. Cancer Res. 1980 Mar;40(3):567–572. [PubMed] [Google Scholar]
  14. Speyer J. L., Sugarbaker P. H., Collins J. M., Dedrick R. L., Klecker R. W., Jr, Myers C. E. Portal levels and hepatic clearance of 5-fluorouracil after intraperitoneal administration in humans. Cancer Res. 1981 May;41(5):1916–1922. [PubMed] [Google Scholar]
  15. Stehlin J. S., Giovanella B. C., de Ipolyi P. D., Muenz L. R., Anderson R. F. Results of hyperthermic perfusion for melanoma of the extremities. Surg Gynecol Obstet. 1975 Mar;140(3):339–348. [PubMed] [Google Scholar]
  16. Stehlin J. S., Jr, Giovanella B. C., de Ipolyi P. D., Anderson R. F. Results of eleven years' experience with heated perfusion for melanoma of the extremities. Cancer Res. 1979 Jun;39(6 Pt 2):2255–2257. [PubMed] [Google Scholar]
  17. Sugarbaker E. V., McBride C. M. Survival and regional disease control after isolation-perfusion for invasive stage I melanoma of the extremities. Cancer. 1976 Jan;37(1):188–198. doi: 10.1002/1097-0142(197601)37:1<188::aid-cncr2820370127>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES