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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2018, Number 6

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Rev Invest Clin 2018; 70 (6)

The effect of single-dose intraperitoneal bevacizumab on peritoneal adhesion formation

Acun G, Ozdemir H, Sunamak O, Unal OZ, Baskan E, Yazi M, Savas B, Berberoglu U

Language: English
References: 30
Page: 279-284
PDF size: 185.21 Kb.


ABSTRACT

Background: Intra-abdominal adhesions and their complications following abdominal surgery are serious problems, with an incidence of 67-93%. Prevention of peritoneal adhesion formation may eliminate the need for surgical intervention, decreasing complications, morbidity, and cost. Bevacizumab is a recombinant monoclonal antibody which specifically binds vascular endothelial growth factor, an important cytokine in adhesion formation, and neutralizes its biological activity. We developed an experimental model in rats to determine the effect of bevacizumab in preventing adhesion formation and analyzed its effect both micro- and macroscopically. Methods: We used 32 Wistar rats randomly divided into two groups: Group A (control) and Group B (bevacizumab), with 16 rats each. A modified cecum abrasion model was developed; 0.9% NaCl solution was administered intraperitoneally to Group A and bevacizumab to Group B. On day 15, adhesion formation was evaluated both macro- and microscopically. Results: Both micro- and macroscopic adhesion grades in Group B were significantly lower than those of control Group A; macroscopic grades were 2.69 ± 0.95 and 0.69 ± 0.8, and microscopic grades were 2.25 ± 1.06 and 0.5 ± 0.52 for Groups A and B, respectively. Conclusions: Bevacizumab was effective in preventing intraperitoneal adhesion formation in our study; however, its inhibitory effects on embryogenesis and the hematopoietic, endocrine, and immune systems may limit its clinical use.


REFERENCES

  1. ten Broek RP, Bakkum EA, Laarhoven CJ, van Goor H Epidemiology and prevention of postsurgical adhesions revisited. Ann Surg. 2016;263:12-9.

  2. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions; etiology, pathophysiology, and clinical significance. Dig Surg. 2001;18:260-73.

  3. Morawski B, Nawrot I, Klonowski W, Mądrecki M, Tarnowski W. Peritoneal adhesions as a cause of mechanical small bowel obstruction based on own experience. Pol Przegl Chir. 2015;86: 523-31.

  4. Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol. 2011;17:4545-53.

  5. Makarchian HR, Kasraianfard A, Ghaderzadeh P, Javadi SM, Ghorbanpoor M. The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats. Acta Cir Bras. 2017;32:22-7.

  6. Cassidy MR, Sheldon HK, Gainsbury ML, et al. The neurokinin 1 receptor regulates peritoneal fibrinolytic activity and postoperative adhesion formation. J Surg Res. 2014;191:12-8.

  7. Giusto G, Beretta G, Vercelli C, et al. A pectin-honey hydrogel prevents postoperative intraperitoneal adhesions in a rat model. BMC Vet Res. 2017;13:55.

  8. De Clercq K, Schelfhout C, Bracke M, et al. Genipin-crosslinked gelatin microspheres as a strategy to prevent postsurgical peritoneal adhesions: in vitro and in vivo characterization. Biomaterials. 2016;96:33-46.

  9. Poehnert D, Grethe L, Maegel L, et al. Evaluation of the effectiveness of peritoneal adhesion prevention devices in a rat model. Int J Med Sci. 2016;13:524-32.

  10. Diamond MP, El-Hammady E, Munkarah A, Bieber EJ, Saed G. Modulation of the expression of vascular endothelial growth factor in human fibroblasts. Fertil Steril. 2005;83:405-9.

  11. Kalofonos HP, Grivas PD. Monoclonal antibodies in the management of solid tumors. Curr Top Med Chem. 2006;6: 1687-705.

  12. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19:843-50.

  13. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-42.

  14. Chiang SC, Cheng CH, Moulton KS, Kasznica JM, Moulton SL. TNP-470 inhibits intraabdominal adhesion formation. J Pediatr Surg. 2000;35:189-96.

  15. Greene AK, Alwayn IP, Nose V, et al. Prevention of intra-abdominal adhesions using the antiangiogenic COX-2 inhibitor celecoxib. Ann Surg. 2005;242:140-6.

  16. Ignjatovic D, Aasland K, Pettersen M, et al. Intra- abdominal administration of bevacizumab diminishes intra-peritoneal adhesions. Am J Surg. 2010;200:270-5.

  17. Zuhlke HV, Lorenz EM, Straub EM, Savvas V. Pathophysiology and classification of adhesions. Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir. 1990;1:1009-16.

  18. Fredriksson F, Sellberg F, Bowden T, Engstrand T, Berglund D, Lilja HE. Sutures impregnated with carbazate-activated polyvinyl alcohol reduce intraperitoneal adhesions. J Pediatr Surg. 2017;52:1853-8.

  19. Brochhausen C, Schmitt VH, Mamilos A,et al. Expression of CD68 positive macrophages in the use of different barrier materials to prevent peritoneal adhesions-an animal study. J Mater Sci Mater Med. 2017;28:15.

  20. Koninckx PR, Gomel V. Introduction: quality of pelvic surgery and postoperative adhesions. Fertil Steril. 2016;106:991-3.

  21. Conze J, Junge K, Klinge U, et al. Intraabdominal adhesion formation of polyprolene mesh. Influence of coverage of omentum and polyglactin. Surg Endosc. 2005;19:798-803.

  22. Bikfalvi A. Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor-4 and the VEGF/ VEGFR system. Biochem Pharmacol. 2004;68:1017-21.

  23. Costache MI, Iordache S, Costache CA, Dragos E, Dragos A, Saftoiu A. Molecular analysis of vascular endothelial growth factor (VEGF) receptors in EUS-guided samples obtained from patients with pancreatic adenocarcinoma. J Gastrointestin Liver Dis. 2017;26:51-7.

  24. Beddy D, Watson RW, Fitzpatrick JM, O’Connell PR. Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn’s disease. Br J Surg. 2004;91:72-7.

  25. Henry CR, Sisk RA, Tzu JH, et al. Long-term follow-up of intravitreal bevacizumab for the treatment of pediatric retinal and choroidal diseases. JAAPOS. 2015;19:541-8.

  26. Wang JK, Su PY, Hsu YR, Chen YJ, Chen FT, Tseng YY. Comparison of the efficacy of intravitreal aflibercept and bevacizumab for macular edema secondary to branch retinal vein occlusion. J Ophthalmol. 2016;2016:8421940.

  27. Gordon MS, Cunningham D. Managing patients treated with bevacizumab combination therapy. Oncology. 2005;69:25-33.

  28. Moraloglu O, Işik H, Kiliç S, et al. Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity. Fertil Steril. 2011; 95:2638-41.

  29. Jordan K, Luetkens T, Gog C, et al. Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: a multicentre double-blind, placebocontrolled phase II study-AIO SUP-0108. Eur J Cancer. 2016;63:127-34.

  30. Maggiore UL, Bellati F, Ruscito I, et al. Monoclonal antibodies therapies for ovarian cancer. Expert Opin Biol Ther. 2013;13: 739-64.




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