Colonic anastomosis with a doxycycline-coated stent: an experimental study in a porcine model.
BACKGROUND
Matrix metalloproteinases (MMPs) are supposed to be potential drug targets to prevent leakage after colonic anastomosis. A method of colonic anastomosis by using a stent coated with doxycycline, a MMP inhibitor, was developed and its safety and feasibility, as well as the effect of locally regulating MMPs, were evaluated by comparing with the conventional method or the method with a doxycycline-free stent.


METHODS
48 pigs were assigned randomly to doxycycline-coated stent anastomosis group (DSA), doxycycline-free stent anastomosis group (SA), or conventional anastomosis group (CA). In each group, pigs were subdivided into four subgroups according to postoperative observation time (3, 7, 14, and 30 days). Healing of anastomosis and expressions of MMP-2/9 were evaluated.


RESULTS
No anastomotic leakage, stricture or necrosis was observed in the DSA group. No significant difference of bursting pressure was found between the DSA group and SA group. Relative expression of MMP-2 in the DSA group was significantly lower than in the SA group on postoperative days 3 and 7. No significant differences of hydroxyproline content, microvessel density and TGF-β1 level were found in these groups.


CONCLUSIONS
These results suggested this method was feasible and safe for colonic anastomosis with the advantage of locally inhibiting MMPs.
Department of Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
YiFan
Y
Wang
XiaoYan
X
Cai
JinHua
J
Mei
Kun
K
Liu
XiuJun
X
Cai
D000714:Anastomosis, Surgical / Q000009:adverse effects; D057868:Anastomotic Leak / Q000517:prevention & control; D000818:Animals; D003106:Colon / Q000601:surgery*; D004318:Doxycycline / Q000008:administration & dosage*; D054855:Drug-Eluting Stents; D005240:Feasibility Studies; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage*; D055806:Microvessels / Q000033:anatomy & histology; D011312:Pressure / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline; D006909:Hydroxyproline