Abstract
There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess it potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P < 0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.
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Selected References
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- Buyse M., Zeleniuch-Jacquotte A., Chalmers T. C. Adjuvant therapy of colorectal cancer. Why we still don't know. JAMA. 1988 Jun 24;259(24):3571–3578. [PubMed] [Google Scholar]
- Circolo A., Welgus H. G., Pierce G. F., Kramer J., Strunk R. C. Differential regulation of the expression of proteinases/antiproteinases in fibroblasts. Effects of interleukin-1 and platelet-derived growth factor. J Biol Chem. 1991 Jul 5;266(19):12283–12288. [PubMed] [Google Scholar]
- Cunliffe W. J., Sugarbaker P. H. Gastrointestinal malignancy: rationale for adjuvant therapy using early postoperative intraperitoneal chemotherapy. Br J Surg. 1989 Oct;76(10):1082–1090. doi: 10.1002/bjs.1800761030. [DOI] [PubMed] [Google Scholar]
- Fisher B., Gunduz N., Saffer E. A. Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983 Apr;43(4):1488–1492. [PubMed] [Google Scholar]
- Glimelius B., Påhlman L. The value of adjuvant therapy after radical surgery for colorectal cancer. Ann Med. 1992 Feb;24(1):9–14. doi: 10.3109/07853899209164139. [DOI] [PubMed] [Google Scholar]
- Graf W., Weiber S., Glimelius B., Jiborn H., Påhlman L., Zederfeldt B. Influence of 5-fluorouracil and folinic acid on colonic healing: an experimental study in the rat. Br J Surg. 1992 Aug;79(8):825–828. doi: 10.1002/bjs.1800790840. [DOI] [PubMed] [Google Scholar]
- Graf W., Westlin J. E., Påhlman L., Glimelius B. Adjuvant intraperitoneal 5-fluorouracil and intravenous leucovorin after colorectal cancer surgery: a randomized phase II placebo-controlled study. Int J Colorectal Dis. 1994 Apr;9(1):35–39. doi: 10.1007/BF00304298. [DOI] [PubMed] [Google Scholar]
- Harris D. T., Mastrangelo M. J. Theory and application of early systemic therapy. Semin Oncol. 1991 Dec;18(6):493–503. [PubMed] [Google Scholar]
- Hasty K. A., Pourmotabbed T. F., Goldberg G. I., Thompson J. P., Spinella D. G., Stevens R. M., Mainardi C. L. Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases. J Biol Chem. 1990 Jul 15;265(20):11421–11424. [PubMed] [Google Scholar]
- Hendriks T., Mastboom W. J. Healing of experimental intestinal anastomoses. Parameters for repair. Dis Colon Rectum. 1990 Oct;33(10):891–901. doi: 10.1007/BF02051930. [DOI] [PubMed] [Google Scholar]
- Hesp F. L., Hendriks T., Lubbers E. J., deBoer H. H. Wound healing in the intestinal wall. A comparison between experimental ileal and colonic anastomoses. Dis Colon Rectum. 1984 Feb;27(2):99–104. doi: 10.1007/BF02553985. [DOI] [PubMed] [Google Scholar]
- Högström H., Haglund U., Zederfeldt B. Suture technique and early breaking strength of intestinal anastomoses and laparotomy wounds. Acta Chir Scand. 1985;151(5):441–443. [PubMed] [Google Scholar]
- Kemeny N., Lokich J. J., Anderson N., Ahlgren J. D. Recent advances in the treatment of advanced colorectal cancer. Cancer. 1993 Jan 1;71(1):9–18. doi: 10.1002/1097-0142(19930101)71:1<9::aid-cncr2820710104>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Kimball E. S., Schneider C. R., Fisher M. C., Clark M. C. Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages. J Leukoc Biol. 1992 Sep;52(3):349–356. doi: 10.1002/jlb.52.3.349. [DOI] [PubMed] [Google Scholar]
- Martens M. F., Hendriks T. Postoperative changes in collagen synthesis in intestinal anastomoses of the rat: differences between small and large bowel. Gut. 1991 Dec;32(12):1482–1487. doi: 10.1136/gut.32.12.1482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martens M. F., Hendriks T., Wobbes T., De Pont J. J. Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6. Br J Cancer. 1992 May;65(5):649–654. doi: 10.1038/bjc.1992.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martens M. F., de Man B. M., Hendriks T., Goris R. J. Collagen synthetic capacity throughout the uninjured and anastomosed intestinal wall. Am J Surg. 1992 Oct;164(4):354–360. doi: 10.1016/s0002-9610(05)80904-3. [DOI] [PubMed] [Google Scholar]
- Mayer R. J. Chemotherapy for metastatic colorectal cancer. Cancer. 1992 Sep 1;70(5 Suppl):1414–1424. doi: 10.1002/1097-0142(19920901)70:3+<1414::aid-cncr2820701533>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Nordlinger B., Panis Y., Puts J. P., Herve J. P., Delelo R., Ballet F. Experimental model of colon cancer: recurrences after surgery alone or associated with intraperitoneal 5-fluorouracil chemotherapy. Dis Colon Rectum. 1991 Aug;34(8):658–663. doi: 10.1007/BF02050346. [DOI] [PubMed] [Google Scholar]
- Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
- Stevenson H. C., Green I., Hamilton J. M., Calabro B. A., Parkinson D. R. Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer. J Clin Oncol. 1991 Nov;9(11):2052–2066. doi: 10.1200/JCO.1991.9.11.2052. [DOI] [PubMed] [Google Scholar]
- Sugarbaker P. H., Graves T., DeBruijn E. A., Cunliffe W. J., Mullins R. E., Hull W. E., Oliff L., Schlag P. Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res. 1990 Sep 15;50(18):5790–5794. [PubMed] [Google Scholar]
- Sugarbaker P. H. Intraperitoneal chemotherapy for treatment and prevention of peritoneal carcinomatosis and sarcomatosis. Dis Colon Rectum. 1994 Feb;37(2 Suppl):S115–S122. doi: 10.1007/BF02048443. [DOI] [PubMed] [Google Scholar]
- Windle R., Bell P. R., Shaw D. Five year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer. Br J Surg. 1987 Jul;74(7):569–572. doi: 10.1002/bjs.1800740707. [DOI] [PubMed] [Google Scholar]
- de Roy van Zuidewijn D. B., Hendriks T., Wobbes T., de Boer H. H. Intraperitoneal cytostatics impair healing of experimental intestinal anastomoses. Br J Cancer. 1991 Jun;63(6):937–941. doi: 10.1038/bjc.1991.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Waard J. W., Wobbes T., Hendriks T. Early post-operative 5-fluorouracil does not affect the healing of experimental intestinal anastomoses. Int J Colorectal Dis. 1993 Sep;8(3):175–178. doi: 10.1007/BF00341194. [DOI] [PubMed] [Google Scholar]
