Systemic and peritoneal inflammatory response after laparoscopic-assisted gastrectomy and the effect of inflammatory cytokines on adhesion of gastric cancer cells to peritoneal mesothelial cells

Abstract

There still remain concerns over the potential for peritoneal metastasis after laparoscopic surgery. We designed this trial to investigate the effects of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the interaction between gastric cancer cells and mesothelial cells, and to evaluate differences in both the peritoneal and systemic cytokine (IL-1β and TNF-α) concentrations after laparoscopic and conventional surgical approaches, thus offering another possible advantage of laparoscopic procedures for treatment of gastric cancer. A reproducible human in vitro assay was developed to study adhesion of SGC-7901 and MKN-45 human gastric cancer cells to monolayers of primary cultured human peritoneal mesothelial cells (HPMCs). Tumor cell adhesion to a mesothelial monolayer was assessed after preincubation of the monolayer with IL-1β and TNF-α using flow cytometry. Expression of adhesion molecules (ICAM-1, VCAM-1, and CD44) and their counterparts (LFA-1 and VLA-4) was investigated by real-time polymerase chain reaction (PCR) immunocytochemical staining. Furthermore, the proinflammatory cytokines IL-1β and TNF-α were measured perioperatively in peritoneal drain fluid and in serum by enzyme immunoassay. Preincubation of the mesothelial monolayer with IL-1β and TNF-α resulted in enhanced tumor cell adhesion of SGC-7901 and MKN-45 cells. Mesothelial cells showed significant enhancement of expression of ICAM-1, VCAM-1, and CD44 after stimulation with IL-1β and TNF-α. Meanwhile their counterparts (LFA-1, VLA-4, and CD44) were identified in gastric cancer cells. The level of IL-1β in peritoneal drain fluid and in serum perioperatively in the laparoscopy-assisted gastrectomy group was lower than in the conventional open gastrectomy group, whereas there were no significant differences between the laparoscopic-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy(CODG) groups with respect to TNF-α. The presented results prove that IL-1β and TNF-α are significant stimulating factors in gastric cancer cell adhesion in vitro and may therefore partly account for local tumor recurrence and peritoneal metastasis in vivo. Owing to less impact on the postoperative abdominal regional and systemic immune responses, laparoscopic surgery not only shows clinically relevant advantages but also causes less effect of inflammatory factors on local recurrence and peritoneal metastasis of gastric cancer than conventional operations. Thus, we offer another possible advantage of laparoscopic procedures for treatment of gastric cancer.