Immunologic parameters during NOTES compared with laparoscopy in a randomized blinded porcine trial

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Abstract
It remains unclear if the natural orifice translumenal endoscopic surgery (NOTES) technique is less invasive than laparoscopy. Serum interleukins and peritoneal cellular response have been utilized to support the immunologic difference between open and laparoscopic surgery. We hypothesized that there would be no difference between cytokine levels during NOTES or laparoscopic peritoneoscopy. Twelve pigs were assigned to NOTES or standard laparoscopy with permuted block randomization. Each group underwent 90 min of diagnostic peritoneoscopy using CO2 for laparoscopy and air for NOTES pneumoperitoneum. Blood draws were obtained at baseline, at procedure end, and on postoperative days (POD) 1, 2, and 7. Quantification of cytokines (IL-1b and TNF-α) was performed with a Duo Set Porcine enzyme-linked immunosorbent assay (ELISA). Laboratory results were captured by a technician blinded to the research question, and data analysis was performed by an investigator blinded to the procedure using t-test and repeated measures linear model. The study was approved by the institutional animal care and use committee (IACUC). All procedures were successfully completed. One NOTES animal succumbed to hemorrhagic gastritis (day 3). All other animals thrived to POD 14, with no gross infections at necropsy. Animals undergoing laparoscopy had lower mean arterial pH than NOTES animals (p < 0.001). Serum and intraperitoneal white blood cell (WBC) counts were similar between the groups. Mean interleukin-1b levels at baseline, at the end of the procedure and at 48 h did not differ (0.50 and 0.31; p = 0.65). TNF-α levels did not differ at baseline or procedure end but increased in the NOTES group on POD 1, persisting to POD 7. Tumor necrosis factor-α (TNF-α) decreased in the laparoscopy group (p = 0.005). Cytokines and WBC did not differ between laparoscopic and NOTES groups during the initial 24 h. These findings do not currently support the assumption that NOTES is less invasive than laparoscopy. The late TNF-α elevation contradicts other studies and requires further examination.