Wei Zhiliang, Tan Bin, Cao Shougen, Liu Shanglong, Tan Xiaojie, Yao Zengwu, Yin Na, Li Jiante, Zhang Dongfeng, Zhou Yanbing
Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Oncotarget. 2017 Jun 27;8(26):43376-43388. doi: 10.18632/oncotarget.14758.
Evidence has shown that neoadjuvant chemotherapy (NACT) is correlated with patients' overall postoperative complications. But investigations on relationship between NACT and postoperative infectious complications, which is closely linked to intestinal barrier damage, were scanty. Accordingly, 90 patients with advanced gastric cancer were included in this study. The differences in postoperative infectious complications were determined between NACT group in which patients received NACT before surgery and SURG group in which received surgical treatment immediately after diagnosis. The damage of mechanical structure of intestinal barrier was assessed by hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemistry. Mucosal microbiota changes were determined by using a 16S rRNA gene sequencing approach. Results showed that the incidence of postoperative infectious complications were significantly higher in the NACT group. Tight junctions were disrupted, and claudin-1, ZO-1 and occludin were down-regulated in patients with infectious complications in overall compared with those without. And similarly, the patients in the NACT group also showed damaged intestinal barrier compared with those in SURG group. Besides, the total diversity of mucosal related bacteria was decreased and relative abundance of some probiotics, such as Bifidobacterium, Faecalibacterium and Ruminococcus, was reduced in the NACT group as well. In conclusion, our study identifies a higher incidence of postoperative infection in gastric cancer patients who underwent NACT treatment, and these changes might be caused by a significant damage in the intestinal barrier as well as reduced probiotics.
有证据表明，新辅助化疗（NACT）与患者术后总体并发症相关。但关于NACT与术后感染性并发症之间关系的研究较少，而术后感染性并发症与肠屏障损伤密切相关。因此，本研究纳入了90例晚期胃癌患者。比较了术前接受NACT的NACT组和诊断后立即接受手术治疗的SURG组术后感染性并发症的差异。通过苏木精-伊红染色、透射电子显微镜和免疫组织化学评估肠屏障机械结构的损伤。采用16S rRNA基因测序方法测定黏膜微生物群的变化。结果显示，NACT组术后感染性并发症的发生率显著更高。与未发生感染性并发症的患者相比，总体上发生感染性并发症的患者紧密连接被破坏，claudin-1、ZO-1和闭合蛋白下调。同样，与SURG组相比，NACT组患者的肠屏障也受损。此外，NACT组黏膜相关细菌的总多样性降低，一些益生菌如双歧杆菌、粪杆菌和瘤胃球菌的相对丰度也降低。总之，我们的研究发现接受NACT治疗的胃癌患者术后感染发生率更高，这些变化可能是由肠屏障的显著损伤以及益生菌减少引起的。
