The effect of gender on early colonic anastomotic wound healing
Magnus S. Ågren
Lars N. Jorgensen
Accepted: 15 May 2018 /Published online: 31 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose Clinically, male patients subjected to colorectal surgery are more prone to develop anastomotic leakage than female
patients by unknown mechanisms. Our aim was to investigate the impact of gender on anastomotic wound healing using an
Methods One-layer colonic anastomosis was constructed in 8-week-old 28 male and 32 female Sprague-Dawley rats. Animals of
one group (n = 30) were sacrificed immediately after surgery day 0 and the other group (n = 30) on postoperative day 3.
Anastomotic breaking strength, total collagen (hydroxyproline), soluble collagen (Sircol), matrix metalloproteinase (MMP)-9,
and transforming growth factor (TGF)-β1 were measured.
Results The anastomotic breaking strength decreased from day 0 to day 3 with no significant gender differences either in the
extent of decline (P =0.122)orabsoluteday3strengths(P = 0.425). Analogously, total collagen concentration in the anastomotic
wounds decreased postoperatively and were lower (P = 0.043) in the male compared with the female rats on day 3. MMP-9 levels
increased in the anastomoses postoperatively, but they did not differ (P = 0.391) between male and female animals. Soluble
collagen levels were lower in the day-3 anastomoses of male versus female rats (P = 0.015) and correlated positively with total
TGF-β1 levels (r
= 0.540, P = 0.006). Although TGF-β1 tended to be lower in male compared with the female rats, the
differences did not reach statistical significance.
Conclusion Our findings point towards a less favorable collagen metabolism in colonic anastomoses of male compared with
female rats during early wound healing.
Keywords Anastomotic leakage
Anastomotic leakage (AL) is a severe complication after colo-
rectal surgery [1, 2]. The pathogenesis of AL is multifactorial.
Procedure-specific risk factors include emergency surgery,
low rectal anastomosis, increased operation time, high blood
loss, blood transfusion, and lack of a protective stoma .
Examples of patient-specific risk factors are high age, preop-
erative radiotherapy, smoking, alcohol abuse, high body mass
index, high American Society of Anesthesiologists score, and
the male gender [4, 5].
Odds ratios of AL in male versus female patients vary from
1.4 to 3.5 after colorectal resection [6, 7]. The increased inci-
dence of AL in males after rectal resection is conventionally
explained by the deeper and narrower male pelvis, making
dissection more difficult than in the female pelvis [8, 9]. In
contrast, Krarup et al.  found that the male gender was an
independent risk factor of AL regardless of the level of the
anastomosis and concluded that the narrow male pelvis was an
irrelevant factor. This indicates the existence of biological
differences between males and females in anastomotic wound
healing, anastomoses constructed in the male intestine being
more vulnerable to dehiscence than anastomoses made in the
female intestine [7, 10].
Early anastomotic strength relies on the suture-holding ca-
pacity of submucosal collagen . After construction of
* Marie Kjaer
Digestive Disease Center, Bispebjerg Hospital, University of
Copenhagen, Copenhagen, Denmark
Department of Drug Design and Pharmacology, Faculty of Health
and Medical Science, University of Copenhagen,
Copenhagen Wound Healing Center, Bispebjerg Hospital, University
of Copenhagen, Copenhagen, Denmark
International Journal of Colorectal Disease (2018) 33:1269–1276