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The Effect of Cyclo-oxygenase Inhibition on Systemic Cytokine-Acute Phase Protein Response After Gastrointestinal Surgery

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Abstract (2. Language): 
Objectives: Surgical operations have been shown to cause a variety of changes in cytokines and acute phase proteins. These changes can be markedly attenuated or prevented by cyclo-oxygenase inhibition. Therefore the authors assessed the effect of piroxicam treatment, having the contradictory results regarding this subject, on cytokine and acute phase protein changes after surgery. Material and methods: The systemic cytokine and acute phase protein responses to major gastrointestinal surgery were studied in 24 patients undergoing elective gastric or rectal surgery. The patients were divided into two groups. Both groups had 12 patients and consisted of six patients undergoing subtotal distal gastrectomy and six patients undergoing low anterior resection. Piroxicam (10 mg, IM), a cyclo-oxygenase inhibitor, was administered to group II patients, but not to group I patients, 12 hour before surgery and 1 and 12 hours after surgery. Blood samples were collected 8 hour before surgery and one and five days after surgery for interleukin-6, tumor necrosis factor-a, C-reactive protein and fibrinogen determinations.a levels in fifth postoperative day were significantly lower (p<0.05) than those in first postoperative day in group II. In contrast, decreased levels were not obtained in group I patients. Conclusion: Piroxicam treatment in the perioperative course is able to reduce cytokine and acute phase protein responses. Therefore, piroxicam may be useful in decreasing the stress response regarding cytokines and acute phase proteins in patients undergoing major gastrointestinal surgery.
Abstract (Original Language): 
Amaç: Cerrahi girişimler sitokin ve akut faz protein yanıtına sebebiyet verirler. Bu yanıt siklooksijenaz inhibisyonuyla önlenebilir. Bu çalışmada cerrahi girişim sonrası sitokin ve akut faz protein yanıtı üzerinde, bu konuyla ilgili çelişkili sonuçlara sahip olan Piroxicam tedavisinin etkin/i/iği incelendi. Materyal ve Metot: Elektif major gastrik veya rektum cerrahisine maruz kalan 24 hastada sistemik sitokin ve akut faz protein yanıtı incelendi. Hastalar 2 gruba ayrıldı. Her 2 grup 12 hastadan ibaret olup, 6' sına subtotal distal gastrektomi, 6' sına ise aşağı anterior rezeksiyon yapıldı. Bir siklooksijenaz inhibitörü olan Piroxicam (10 mg, intramuskuler) Grup I hastalara cerrahiden 12 saat önce ve 1 ile 12 saat sonra olmak üzere toplam 30 mg uygulandı. Grup II hastalara ise Piroxicam uygulanmadı. Cerrahi girişimden 8 saat önce ve 1 ile 5 gün sonra Interleukin-6, Tümör nekrozis faktör alfa, C-reaktif protein ve fibrinojenin serum seviyelerini ölçmek için kan örnekleri alındı. Bulgular: Grup I hastalarda Interleukin-6, Tümör nekrozis faktör alfa, C-reaktif protein ve fibrinojenin postoperatif 5. günkü seviyeleri postoperatif 1. gündeki değerlere göre önemli derecede düşmüştü (p<0.05). Bu farklılıklar Grup II hastalarda görülmedi. Sonuç: Peroperatif dönemdeki Piroxicam tedavisi sitokin ve akut faz protein yanıtını azaltabilir. Bu nedenle Piroxicam tedavisi major gastrointestinal cerrahi girişime maruz kalan hastalarda sitokin ve akut faz protein yanıtını azaltmada faydalı olabilir.



1. Lennard TW, Shenton BK, Borzotta A, Donnely PK, White M, Gerrie LM, Proud G, Taylor RM. The influence of surgical operations on components of the human immune system. Br J Surg 1985; 72: 771-6.
2. Grzelak I, Olszewski WL, Zaleska M, Durlik M, Lagiewska B, Muszynski M, Rowinsky W: Blood cytokine levels rise even after minor surgical trauma. J Clin Immunol 1996; 16: 159-64.
3. Naito Y, Tamai S, Shingu K, Shindo K, Matsui T, Segawa H, Nakai Y, Mori K. Responses of plasma adrenocorticotropic hormone, Cortisol, and cytokines during and after upper abdominal surgery. Anesthesiology 1992; 77: 426-31.
4. Baigrie RJ, Lamont PM, Kwiatkowski D, Dallman MJ, Morris PI Systemic cytokine response after major surgery. Br J Surg 1992; 79: 757-60.
5. Joris J, Cigarini I, Legrand M, Jackuet N, De Groote D, Franchimont P, Lamy M. Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. Br J Anaesth 1992; 69: 341¬5.
6. Parry-Bilings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 1992; 127: 1237-40.
7. Cinat ME, Waxman K, Granger GA, Pearce W, Annas C, Daughters K. Trauma causes sustained elevation of soluble tumor necrosis factor receptors. J Am Coll Surgl994; 179: 529-37.
8. Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci 1990; 79: 161-5.
9. Cruickshank AM, Hansell DT, Burns HJ, Shenkin A. Effect of nutritional status on acute phase protein response to elective surgery. Br J Surg 1989; 76: 165-8.
10. Hasselgren PO, Pederson P, Sax HC, Warner BW, Fischer JE. Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis. Arch Surg 1988;123: 992-9.
11. Schulze S, Sommer P, Bigler D, Honnens M, Shenkin A, Cruickshank AM, Bukhave K, Kehlet H. Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery. Arch Surg 1992; 127: 325-31.
12. Lin E, Lowry SF, Calvano SE. The systemic response to injury. ImSchwartz SI, editor: Principles of Surgery. New York: McGraw-Hill 1999: 3-51.
13. Revhaug A, Michie HR, Manşon JM, Watters JM, Dinarello CA, Wolff SM, Wilmore DW. Inhibition of cyclo-oxygenase attenuates the metabolic response to endoxin in humans. Arch Surg 1988; 123:162¬70
14. Chambrier C, Chassard D, Bienvenu J, Saudin F, Paturel B, Garrigue C, Barbier Y, Paul Bouletreau P: Cytokine and hormonal changes after cholecystectomy : Effect of Ibuprofen pretreatment. Ann Surg 1996; 224: 178-82.
15. Ruhi A, Berezin I, Colins SM. Involvement of eicosanoids and macrophage-like cells in cytokine-mediated changes in rat myenteric nerves. Gastroenterol 1995; 109: 1852-62.
16. Eberlein TJ, Schoof DD, Michie HR, Massaro AF, Burger U, Wilmore DW, Wilson RE. Ibuprofen causes reduced toxic effects of interleukin-2 administration in patients with metastatic cancer. Arch Surg 1989; 124: 542-7.
17. Michie HR, Majzoub JA, O'Dwyer ST, Revhaug A, Wilmore DW. Both cyclooxygenase-dependent and cyclooxygenase-independent pathways mediate the neuroendocrin response in humans. Surg 1990; 108: 254-9.
18. Berg J, Fellier H, Cristoph T, Grarup J, Stimmeder D. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-l/-2, inducible nitric oxide synthase (İNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res 1999; 48: 369-79.
19. McNiff PA, Laliberte RE, Svensson L, Pazoles CJ, Gabel CA. Inhibition of cytokine activation processes in vitro by tenidap, a novel antiinflammatory agent. Cytokine 1995; 7: 196-208.
20. Patel RT, Deen KI, Youngs D, Warwick J, Keighley MR. Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis. Br J Surg 1994; 81: 1306-08
21. Damas P, Canivet JL, de Groote D, Vrindts Y, Albert A, Franchimont P, Lamy M. Sepsis and serum cytokine concentrations. Crit Care Med 1997; 25: 405-12.
22. Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JW, Endres S, Lonnemann G, Corsetti J, Chernow B, et al. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis 1990; 161: 79-84.
23. Boermeester MA, van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995;130: 739-48.
24. Boermeester MA, Straatsburg IH, Houdijk AP, Meyer C, Fredeeriks WM, Wesdorp RI, van Noorden CJ, van Leeuwen PA. Endotoxin and interleukin-1 related hepatic inflammatory response promotes liver failure after partial hepatectomy. Hepatology 1995; 22: 1499-506.
25. van Berge Henegouwen MI, van der Poll T, van Deventer SJ, Gouma DJ. Peritoneal cytokine release after elective gastrointestinal surgery and postoperative complications. Am J Surg 1998; 175: 311-6.
26. van der Poll T, van Deventer SJ, Hack CE, Wolbink GJ, Aarden LA, Buller HR, ten Cate JW. Effects on leukocytes after injection of tumor necrosis factor into healthy humans. Blood 1992; 79: 693-8.
27. Cheng JB, Watson JW, Pazoles CJ, Eskra JD, Griffiths RJ, Cohan VL, Turner CR, Showell HJ, Pettipher ER. The phosphodiesterase type 4 (PDE4 inhibitor CP-80,633 elevates plasma cyclic AMP levels and decreases tumor necrosis factor-alpha (TNF alpha) production in mice: effect of adrenalectomy. J Pharmacol ExpTher 1997; 280:621-6.
28. McMillen MA, Huribal M, Sumpio B. Common pathway of endothelial-leukocyte interaction in shock, ischemia, and reperfusion. Am J Surg 1993; 166: 557-62

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