Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1984 Jun;199(6):782–790. doi: 10.1097/00000658-198406000-00017

Experimental and clinical observations of the effects of cytotoxic chemotherapeutic drugs on wound healing.

K I Bland, W E Palin, J A von Fraunhofer, R R Morris, R A Adcock, G R Tobin 2nd
PMCID: PMC1353468  PMID: 6732317

Abstract

The administration of perioperative doxorubicin HCl (Adriamycin) had profound effects on wound healing for 5 out of 7 breast cancer patients and 5 of 5 melanoma patients following intravenous and intra-arterial infusional chemotherapy, respectively. The clinical observation of significant reduction in wound tear strength (WTS) and wound tear energy ( WTE ) in the group of patients with cutaneous melanoma initiated this experimental analysis. A study of WTS ( kNm -2) in nontumor-bearing (non-TB) and Morris Hepatoma (MH)-7777 (TB) rats treated with therapeutic doses of Adriamycin (ADR) and methotrexate (MTX) was compared with saline-treated controls. Mean tumor volume (cm3) was unaffected by MTX, while significant tumor inhibition (p less than 0.01) was evident for ADR-treated TB animals. A correlation (r = 0.516, p less than 0.01) was observed for tumor volume and WTS. Separate analysis of TB and non-TB animals identified a significant correlation (r = 0.6259, p less than 0.01) between advancing cachexia in TB rats and WTS. A 21-day analysis was done for 160 animals to determine the effect of MTX and ADR on WTS ( kNm -2) and WTE ( Ncm -1). The presence of MH-7777 significantly (p less than 0.01) reduced WTE for TB animals not treated with chemotherapy. TB animals treated with ADR had significant (p less than 0.01) improvement in WTE at day 21 compared with TB controls. This enhancement in WTE was not observed in rats treated with MTX. These clinical and experimental observations suggest significant retardation of the early phases of wound fibroplasia as determined by WTS and WTE following operative trauma and subsequent administration of therapeutic dosages of cytotoxic agents.

Full text

PDF
785

Selected References

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

  1. Aisner J., Morris D., Elias E. G., Wiernik P. H. Mastectomy as an adjuvant to chemotherapy for locally advanced or metastatic breast cancer. Arch Surg. 1982 Jul;117(7):882–887. doi: 10.1001/archsurg.1982.01380310008003. [DOI] [PubMed] [Google Scholar]
  2. Ariyan S., Kraft R. L., Goldberg N. H. An experimental model to determine the effects of adjuvant therapy on the incidence of postoperative wound infection: II. Evaluating preoperative chemotherapy. Plast Reconstr Surg. 1980 Mar;65(3):338–345. doi: 10.1097/00006534-198003000-00010. [DOI] [PubMed] [Google Scholar]
  3. Bland K. I., Hodge K. M., Bean R. J., Akin J. R., Fry D. E. Effects of systemic hyperthermia on the growth patterns of experimental neoplasms. Surgery. 1982 Apr;91(4):452–458. [PubMed] [Google Scholar]
  4. Cohen S. C., Gabelnick H. L., Johnson R. K., Goldin A. Effects of antineoplastic agents on wound healing in mice. Surgery. 1975 Aug;78(2):238–244. [PubMed] [Google Scholar]
  5. Cohen S. C., Gabelnick H. L., Johnson R. K., Goldin A. Effects of cyclophosphamide and adriamycin on the healing of surgical wounds in mice. Cancer. 1975 Oct;36(4):1277–1281. doi: 10.1002/1097-0142(197510)36:4<1277::aid-cncr2820360413>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  6. Cohn I., Jr Complications and toxic manifestations of surgical adjuvant chemotherapy for breast cancer. Surg Gynecol Obstet. 1968 Dec;127(6):1201–1209. [PubMed] [Google Scholar]
  7. DESPREZ J. D., KIEHN C. L. The effects of cytoxan (cyclophosphamide) on wound healing. Plast Reconstr Surg Transplant Bull. 1960 Sep;26:301–308. doi: 10.1097/00006534-196009000-00005. [DOI] [PubMed] [Google Scholar]
  8. Devereux D. F., Kent H., Brennan M. F. Time dependent effects of adriamycin and x-ray therapy on wound healing in the rat. Cancer. 1980 Jun 1;45(11):2805–2810. doi: 10.1002/1097-0142(19800601)45:11<2805::aid-cncr2820451115>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  9. Dwight R. W., Higgins G. A., Keehn R. J. Factors influencing survival after resection in cancer of the colon and rectum. Am J Surg. 1969 Apr;117(4):512–522. doi: 10.1016/0002-9610(69)90010-5. [DOI] [PubMed] [Google Scholar]
  10. Goldman L. I., Lowe S., al-Saleem T. Effect of fluorouracil on intestinal anastomoses in the rat. Arch Surg. 1969 Mar;98(3):303–304. doi: 10.1001/archsurg.1969.01340090079011. [DOI] [PubMed] [Google Scholar]
  11. Hunt T. K. Disorders of wound healing. World J Surg. 1980 May;4(3):271–277. doi: 10.1007/BF02393382. [DOI] [PubMed] [Google Scholar]
  12. KAISER G. A., HERTER F. P., MALM J. R., DEMETZ A., CAMPIONE M. P. Effects of chemotherapeutic agents administered by isolated perfusion upon wound healing. Surgery. 1961 Jun;49:745–750. [PubMed] [Google Scholar]
  13. Karakousis C. P., Kanter P. M., Park H. C., Sharma S. D., Moore R., Ewing J. H. Tourniquet infusion versus hyperthermic perfusion. Cancer. 1982 Mar 1;49(5):850–858. doi: 10.1002/1097-0142(19820301)49:5<850::aid-cncr2820490505>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  14. Karakousis C. P., Rao U., Holtermann O. A., Kanter P. M., Holyoke E. D. Tourniquet infusion chemotherapy in extremities with malignant lesions. Surg Gynecol Obstet. 1979 Oct;149(4):481–490. [PubMed] [Google Scholar]
  15. Lindstedt E., Sandblom P. Wound healing in man: tensile strength of healing wounds in some patient groups. Ann Surg. 1975 Jun;181(6):842–846. doi: 10.1097/00000658-197506000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morris D., Aisner J., Elias E. G., Wiernik P. H. Mastectomy as an adjunct to combination chemotherapy. Arch Surg. 1978 Mar;113(3):282–284. doi: 10.1001/archsurg.1978.01370150054009. [DOI] [PubMed] [Google Scholar]
  17. Mullen B. M., Mattox D. E., Von Hoff D. D., Hearne E. M. The effect of preoperative adriamycin and dihydroxyanthracenedione on wound healing. Laryngoscope. 1981 Sep;91(9 Pt 1):1436–1443. [PubMed] [Google Scholar]
  18. Perloff M., Lesnick G. J. Chemotherapy before and after mastectomy in stage III breast cancer. Arch Surg. 1982 Jul;117(7):879–881. doi: 10.1001/archsurg.1982.01380310005002. [DOI] [PubMed] [Google Scholar]
  19. Ravitch M. M. Observations on the healing of wounds of the intestines. Surgery. 1975 May;77(5):665–673. [PubMed] [Google Scholar]

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

RESOURCES