Early Postoperative Oral Intake Accelerates Upper Gastrointestinal Anastomotic Healing : Its underlying mechanism and clinical application

基础研究：在我们以前的研究中，我们报道了术后早期经口喂养加速大鼠上消化道吻合口愈合。为了研究其潜在的机制，我们进行了体内和体外实验。将接受近端空肠吻合的大鼠分为4组：肠内营养（EN）组通过胃造口喂养，完全胃肠外营养（TPN）组通过静脉导管喂养，TPN +生理盐水组通过胃造口额外给予生理盐水溶液，TPN +水组通过胃造口额外给予蒸馏水。术后5 d测定吻合口破裂压（ABP）和吻合口组织羟脯氨酸含量。在体外环境中，大鼠胃肠道成纤维细胞进行单轴拉伸60分钟，和I型和III型胶原mRNA的表达进行了评价。ABP和羟脯氨酸 关于我们 EN组、TPN +生理盐水组、TPN +水组血清总碱含量均显著高于单纯TPN组。I型和III型胶原的mRNA水平增加拉伸刺激。ERK、AKT、STAT3和p38 MAPK的表达也明显增加。这些结果表明，机械负荷在吻合口愈合中起着关键作用。同时，我们研究了富血小板血浆（PRP）对肠吻合口愈合的影响，因为血小板被认为是生长因子的储存载体，在肠吻合口愈合的早期阶段起着关键作用。因此，PRP可能以剂量依赖性方式对肠吻合口愈合产生积极影响，但当其高度浓缩时会产生不良影响（双峰效应）。PRP的基本作用似乎是由血小板本身驱动的。临床应用：基于上述研究，我们提出了以下临床实践设想。只要吻合操作正确，上消化道吻合术后早期经口进食不会对吻合口伤口愈合产生负面影响。与禁食期的肠外营养相比，术后早期口服液体摄入很可能加速上消化道吻合口愈合。我们建议现在是时候考虑废除上消化道手术后的饥饿期了。因此，我们证明了术后早期口服摄入是可行和安全的，以及我们报告的实验环境，也适用于具有高度手术应激的上消化道手术，如食管切除术。少

Basic research : In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments. Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated. The ABP and hydroxyprol … More ine content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group. The mRNA levels of type I and type III collagen were increased by stretch stimulation. In addition, the expression of ERK, AKT, STAT3 and p38 MAPK was significantly observed. These results suggest that mechanical loading plays a key role in anastomotic healing. Collaterally, we examined the effects of platelet-rich plasma (PRP) on intestinal anastomotic healing because platelet is regarded as a storage vehicle of growth factors and plays a key role in the early phase of intestinal anastomotic healing. As a result, PRP might exert positive effects on intestinal anastomotic healing in a dose-dependent manner up to a certain level, but adverse effects occur when it is highly concentrated (bimodal effect). The essential PRP action appears to be driven by the platelets themselves.Clinical application : Based on above-mentioned studies, we delivered the following vision for clinical practice. Provided that anastomosis has been performed correctly, early postoperative oral intake after upper gastrointestinal anastomosis does not have a negative impact on anastomotic wound healing. There is a strong probability that early postoperative oral liquid intake accelerates upper gastrointestinal anastomotic healing compared with parenteral nutrition with a fasting period. We proposed that it is time to consider abolishing a period of starvation after upper gastrointestinal surgery. So, we demonstrated that postoperative early oral intake is feasible and safe as well as the experimental setting reported by us, also in an upper gastrointestinal operation with the high degree of surgical stress such as esophagectomy. Less