Neoadjuvant antiangiogenic therapy with tamoxifen does not impair gastrointestinal anastomotic repair in the rat.
BACKGROUND
Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing.


METHODS
A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content.


RESULTS
Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs. 127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs. 1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03).


CONCLUSIONS
Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes.
McNamara
D A
DA
Royal College of Surgeons in Ireland, Department of Surgery at Beaumont Hospital, Dublin, Eire. dmcnamara@RCSI.ie
Walsh
T N
TN
Kay
E
E
Bouchier-Hayes
David J
DJ
D000714:Anastomosis, Surgical; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D013629:Tamoxifen