Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin

Abstract

Background: Intraabdominal adhesions remain a significant cause of morbidity and mortality. Moreover, intraabdominal adhesions can develop in more than 50% of abdominal operations. Aims: We compared the anti-adhesive effects of two different agents on postoperative adhesion formation in a cecal abrasion model. Study Design: Experimental animal study. Methods: Forty Wistar albino type female rats were anesthetized and underwent laparotomy. Study groups comprised Sham, Control, Mitomycin-C, 4% Icodextrin, and Mitomycin-C +4% Icodextrin groups. Macroscopic and histopathological evaluations of adhesions were performed. Results: The frequencies of moderate and severe adhesions were significantly higher in the control group than the other groups. The mitomycin-C and Mitomycin-C +4% Icodextrin groups were associated with significantly lower adhesion scores compared to the control group and 4% Icodextrin group scores (p=0.002 and p=0.008, respectively). The adhesion scores of the Mitomycin-C group were also significantly lower than those of the 4% Icodextrin group (p=0.008). Conclusion: Despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials.

Keywords

• Cecal abrasion, intraabdominal adhesions, mitomycin-C, 4% icodextrin

Kaynakça

1. 1. Dinsmore RC, Calton WC Jr, Harvey SB, Blaney MW. Prevention of adhesion to polypropylene mesh in a traumatized bowel model. J Am Coll Surg 2000;191:131-6.
2. 2. Ray NF, Larsen JW Jr, Stillman RJ, Jacobs RJ. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet 1993;176:271-6.
3. 3. Diamond MP, Freeman ML. Clinical implications of postsurgical adhesions. Hum Reprod Update 2001;7:567-76.
4. 4. Sulaiman H, Gabella G, Davis MC, Mutsaers SE, Boulos P, Laurent J, et al. Presence and distribution of sensory nerve fibers in human peritoneal adhesions. Ann Surg 2001;234:256-61.
5. 5. Di Zerega GS. Biochemical events in peritoneal tissue repair. Eur J Surg Suppl 1997;577:10-6.
6. 6. Bruggmann D, Tchartchian G, Wallwiener M, Münstedt K, Tinneberg HR, Hackethal A. Intra-abdominal adhesions: definition, origin, significance in surgical practice, and treatment options. Dtsch Arztebl Int 2010;107:769-75.
7. 7. Milligan DW, Raftery AT. Observations on the pathogenesis of peritoneal adhesions: a light and electron microscopical study. Br J Surg 1974;61:274-80.
8. 8. Cruz OA. Evaluation of Mitomycin to limit postoperative adhesions in strabismus surgery. J Pediatr Ophthalmol Strabismus 1996;33:89-92.

9. 9. Mahindrakar A, Tandon R, Menon V, Sharma P, Khokhar S. Effectiveness of mitomycin C in reducing reformation of adhesions following surgery for restrictive strabismus. J Pediatr Ophthalmol Strabismus 2001;38:131-5.
10. 10. Cubukçu A, Alponat A, Gönüllü NN, Ozkan S, Erçin C. An experimental study evaluating the effect of mitomycin C on the prevention of postoperative intraabdominal adhesions. J Surg Res 2001;96:163-6.
11. 11. Brown CB, Luciano AA, Martin D, Peers E, Scrimgeour A, diZerega GS; Adept Adhesion Reduction Study Group. Adept (icodextrin 4% solution) reduces adhesions after laparoscopic surgery for adhesiolysis: a doubleblind, randomized, controlled study. Fertil Steril 2007;88:1413-26.
12. 12. Nair SK, Bhat IK, Aurora AL. Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg 1974;108:849-53.
13. 13. Zühlke HV, Lorenz EM, Straub EM, Savvas V. Pathophysiology and classification of adhesions. Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir 1990:1009-16.
14. 14. Parker MC, Wilson MS, Menzies D, Sunderland G, Thompson JN, Clark DN, et al; Surgical and Clinical Adhesions Research (SCAR) Group. Colorectal surgery: the risk and burden of adhesion-related complications. Colorectal Dis 2004;6:506-11.
15. 15. Catena F, Ansaloni L, Lauro A, Ercolani G, D'Alessandro L, Pinna A. Prospective controlled randomized trial on prevention of postoperative abdominal adhesions by Icodextrin 4% solution after laparotomic operation for small bowel obstruction caused by adherences [POPA study: Prevention of Postoperative Adhesions on behalf of the World Society of Emergency Surgery]. Trials 2008;9:74.
16. 16. Diamond MP, Burns EL, Accomando B, Mian S, Holmdahl L. Seprafilm® adhesion barrier: (1) a review of preclinical, animal, and human investigational studies. Gynecol Surg 2012;9:237-45.
17. 17. Conze J, Junge K, Klinge U, Weiss C, Polivoda M, Oettinger AP, et al. Intraabdominal adhesion formation of polypropylene mesh. Influence of coverage of omentum and polyglactin. Surg Endosc 2005;19:798-803.
18. 18. Tander B, Bicakci U, Kilicoglu-Aydin B, Ariturk E, Rizalar R, Bernay F. Antiadhesive effects of mitomycin C and streptopeptidase A in rats with intraperitoneal adhesions. Pediatr Surg Int 2007;23:785-8.
19. 19. Mudhol RR, Zingade ND, Mudhol RS, Harugop AS, Das AT. Prospective randomized comparison of mitomycin C application in endoscopic and external dacryocystorhinostomy. Indian J Otolaryngol Head Neck Surg 2013;65(Suppl 2):255-9.
20. 20. Cengiz Y, Altintas O, Manav Ay G, Cağlar Y. Comparison of the effectiveness of mitomycin-C and Viscoat on delayed adjustable strabismus surgery in rabbits. Eur J Ophthalmol 2005;15:530-5.
21. 21. Narsani AK, Nagdev PR, Memon MN. Outcome of recurrent pterygium with intraoperative 0.02% mitomycin C and free flap limbal conjunctival autograft. J Coll Physicians Surg Pak 2013;23:199-202.
22. 22. Verco SJ, Peers EM, Brown CB, Rodgers KE, Roda N, diZerega G. Development of a novel glucose polymer solution (icodextrin) for adhesion prevention: pre-clinical studies. Hum Reprod 2000;15:1764-72.
23. 23. Catena F, Ansaloni L, Di Saverio S, Pinna AD; World Society of Emergency Surgery. P.O.P.A. study: prevention of postoperative abdominal adhesions by icodextrin 4% solution after laparotomy for adhesive small bowel obstruction. A prospective randomized controlled trial. J Gastrointest Surg 2012;16:382-8.
24. 24. Hwang HJ1, An MS, Ha TK, Kim KH, Kim TH, Choi CS, et al. All the commercially available adhesion barriers have the same effect on adhesion prophylaxis?; Acomparison of barrier agents using a newly developed, severe intra-abdominal adhesion model. Int J Colorectal Dis 2013;28:1117- 25.
25. 25. Ditzel M, Deerenberg EB, Komen N, Mulder IM, Jeekel H, Lange JF. Postoperative adhesion prevention with a new barrier: an experimental study. Eur Surg Res 2012;48:187-93.
26. 26. Bellon JM, Rodriguez M, Garcia-Honduvilla N, Pascual G, Bujan J. Efficiency of 4% icodextrin in preventing adhesions to spiral tacks used to fix intraperitoneal prostheses. Eur Surg Res 2006;38:458-63.
27. 27. Kaptanoglu L, Kucuk HF, Yegenoglu A, Uzun H, Eser M, Mentes CV, et al. Effects of seprafilm and heparin in combination on intra-abdominal adhesions. Eur Surg Res 2008;41:203-7.
28. 28. Irkorucu O, Ferahköşe Z, Memiş L, Ekinci O, Akin M. Reduction of postsurgical adhesions in a rat model: a comparative study. Clinics (Sao Paulo) 2009;64:143-8.