Peritoneal Transforming Growth Factor Beta-1 Expression During Prolonged Laparoscopic Procedures Mare M.A. Lensvelt, MD, 1 Walter J.A. Brokelman, MD, 2 Marie-Louise Ivarsson, MD, PhD, 3 Peter Falk, PhD, 3 and Michel M.P.J. Reijnen, MD, PhD 1 Abstract Background: Laparoscopic surgery may affect peritoneal physiology. Short-term laparoscopic surgery does not affect peritoneal transforming growth factor beta (TGF-b1) expression. The current study was conducted to evaluate the hypothesis that prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression. Study Design: In the first study, 24 patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery (CCR) and 12 were operated on laparoscopically (LCR). In the second study, 12 patients undergoing laparoscopic gastric bypass (LGB) surgery for morbid obesity were included. Biopsies of the parietal peritoneum were taken at standardized moments during the procedures. Tissue con- centrations of active and total TGF-b1 were measured by using enzyme-linked immunosorbent assays. Results: During the LCR, there was a significant increase in peritoneal active TGF-b1 levels (P < 0.05). A similar, but not significant, trend was observed during the CCR. A similar pattern was seen in the total TGF-b1 con- centrations during both procedures. The LGB procedure did not affect peritoneal active or total TGF-b1 con- centrations. During the procedure, both the active and total TGF-b1 levels were significantly higher in the LCR, when compared to the LGB, group (P < 0.05). Conclusions: Prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression, depending on the pro- cedure performed. Considering the role of TGF-b1 in various biologic processes, including adhesiogenesis and oncology, these results may have clinical consequences. Introduction B y minimizing surgical trauma, the minimally invasive character of laparoscopic surgery has led to its broad ac- ceptance. Besides reduced recovery times and improved cosmetics, studies have indicated that endoscopic surgery might also reduce the occurrence of postsurgical peritoneal adhesions. 1–3 Surgical trauma and foreign bodies are the main inducers of adhesions. 4,5 The introduction of a pneumoper- itoneum, however, may also induce adhesion formation after laparoscopic surgery. 6–8 By inducing inflammation, meso- thelial hypoxia is seen as a possible driving mechanism for this adhesion formation. Activation of peritoneal inflammation and modulation of the immune response following laparoscopic surgery even- tually regulates the peritoneal healing processes. Peritoneal mesothelial cells produce multiple cellular mediators, in- cluding transforming growth factor beta (TGF-b) that, in turn, regulates the response of other cells. 9 TGF-b stimulates fibro- blasts to produce many proteins, including collagen, fibro- nectin, and integrins, and decreases the production of proteins whose function is to degrade the extracellular matrix, such as collagenase and heparinase. A variety of studies support the concept that TGF-b is crucial in peritoneal healing and sub- sequent adhesion formation. TGF-b increases the production of plasminogen activator inhibitor and stimulates extracellular matrix deposition, resulting in an accumulation of connective tissue. 10–12 The relation between TGF-b and adhesion forma- tion has been established by various studies demonstrating elevated levels of TGF-b in areas of adhesion formation in humans. 13,14 Additionally, Freeman et al. have shown, in an experimental study, that peritoneal adhesions have increased levels of TGF-b1 and beta3 mRNA transcripts, compared with both uninjured and normally healed peritoneum. 15 In a previous study in patients undergoing a laparoscopic cholecystectomy, we have shown that short-term laparoscopy 1 Department of Surgery, Alysis Zorggroep, Arnhem, The Netherlands. 2 Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands. 3 Department of Surgery, Sahlgrenska University Hospital/O ¨ stra, Go ¨ teborg University, Go ¨ teborg, Sweden. JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 20, Number 6, 2010 ª Mary Ann Liebert, Inc. DOI: 10.1089/lap.2009.0464 545