Enhanced anastomotic healing by Daikenchuto (TJ-100) in rats

Toshiaki Wada,Kenji Kawada,Masayoshi Iwamoto,Kosuke Toda,Kenjiro Hirai,Yoshiharu Sakai,Suguru Hasegawa

doi:10.1038/s41598-018-19550-4

Toshiaki Wada, Kenji Kawada + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-19550-4

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Abstract

Daikenchuto (DKT), a traditional Japanese medicine, is widely used to treat various gastrointestinal disorders. This study aimed to investigate whether DKT could promote the anastomotic healing in a rat model. Pedicled colonic segments were made in left colon by ligation of the feeding arteries, and then intestinal continuity was restored. Colonic blood flow was analyzed by using ICG fluorescence imaging: Fmax, Tmax, T1/2, and Slope were calculated. Anastomotic leakage (AL) was found in 6 of 19 rats (31.6%) in the control group, whereas in 1 of 16 rats (6.2%) in the DKT group. The Fmax and Slope of DKT group were significantly higher than those of control group. DKT could promote the anastomotic healing, with the higher bursting pressure on postoperative day (POD) 2 and 5, the larger granulation thickness on POD 5, and neoangiogenesis on POD 5. Histological examination showed DKT exhibited a decreased inflammatory cell infiltration, enhanced fibroblast infiltration, and enhanced collagen density on POD 5. In the DKT group, the levels of TGFβ1 on POD 2 and VEGFα on POD5 were significantly higher, whereas the level of TNFα on POD 2 was significantly lower. Therefore, DKT could be effective for the prevention of AL following colorectal surgery.

Highlights

Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery and is known to cause high morbidity and mortality
To measure the colonic blood flow, intraoperative indocyanine green (ICG) fluorescence imaging was obtained in all cases
The fluorescence intensity of the pedicle segment was gradually decreasing to the anal side, but the demarcation line determined by ICG fluorescence was not found in this model (Supplementary Fig. 1b)

Summary

Introduction

Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery and is known to cause high morbidity and mortality. ICG is a cyanine dye and its fluorescence imaging is based on the principal that plasma protein-bound ICG emits light with a wavelength of 830 nm when illuminated by NIR light of 760–780 nm It can reveal the presence of an ischemic perfusion before performing the anastomosis. DKT is reported to have three major effects: (i) improvement of intestinal movement, (ii) up-regulation of colonic blood flow, and (iii) activation of anti-inflammatory effect[6,7,8,9]. A randomized, double-blind study on healthy humans in the United States indicated that DKT significantly accelerated intestinal transit in the small intestine and ascending colon[12]. The aim of this study was to investigate whether DKT could promote the anastomotic healing following colorectal surgery in an AL rat model

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