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Hipertermik intraperitoneal kemoterapi uygulanan sıçan modelinde sildenafilin kolon anastomozunu koruyucu etkisi

Year 2025, Volume: 35 Issue: 2, 374 - 381, 30.04.2025
https://doi.org/10.54005/geneltip.1476892

Abstract

Amaç: Çalışmanın amacı hipertermik intraperitoneal kemoterapi uygulanan sıçanlarda kolon anastomozu iyileşmesi üzerine sildenafilin etkilerini araştırmaktır.
Materyal ve Metot: Çalışmamızda 30 adet Wistar-albino cinsi sıçan kullanılmıştır. Sildenafil, kontrol ve sham grubu olmak üzere 3 grupta 10’ar sıçan kullanılmıştır. Tüm gruptaki sıçanlara sol kolon anastomozu yapıldı. Sildenafil grubu ve kontrol grubuna HIPEK işlemi uygulandı. Sildenafil grubuna postoperatif oral sildenafil verildi. 7. gün anastomoz ansı eksize edilerek patlama basıncı ve adezyon değerlendirildi. Anastomoz ansı histopatolojik olarak değerlendirildi. Sonuçlar istatistiksel olarak karşılaştırıldı.
Bulgular: Sonuçlar değerlendirildiğinde patlama basıncı ve adezyon açısından sildenafil grubu ile kontrol grubu arasında fark saptanmamıştır. Sham grubu ise adezyon açısından diğer iki gruba üstün görülmüştür. Histopatolojik incelemede ise sham grubunun anastomoz re-epitelizasyonu ve kas ayrışması açısından diğer iki gruba karşı anlamlı olarak üstün olduğu görülmüştür. Fibrosis ve granülasyon açısından sildenafil grubu ile kontrol grubu arasında anlamlı olarak farklılık saptanmıştır.
Sonuç: HIPEK uygulaması ile beraber yapılan kolon anastomozu üzerinde sildenafilin histopatolojik olarak olumlu etkileri görülmüştür. Kolon anastomozu patlama basınç açısından ise fark görülmemiştir.

References

  • 1. Bruce J, Krukowski ZH, Al-Khairy G, Russell EM, Park KGM. A systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery. British Journal of Surgery [Internet]. 2001;88:1157–68. Available from: www.bjs.co.uk
  • 2. Moran H, Moran BJ, Heald RJ. Anastomotic Leakage After Colorectal Anastomosis. Vol. 18, Seminars in Surgical Oncology. 2000.
  • 3. Pelz JOW, Doerfer J, Decker M, Dimmler A, Hohenberger W, Meyer T. Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Int J Colorectal Dis. 2007 Aug;22(8):941–7.
  • 4. Turaga K, Levine E, Barone R, Sticca R, Petrelli N, Lambert L, et al. Consensus guidelines from the American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States. Ann Surg Oncol. 2014;21(5):1501–5.
  • 5. Uzun H, Konukoglu D, Nuri MK, Ersoy EY, Özçevik S, Yavuz N. The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: Its relationship between nitric oxide and oxidative stress. World J Surg. 2008 Sep;32(9):2107–13.
  • 6. Lee RH, Efron D, Tantry U, Barbul A. Nitric oxide in the healing wound: A time-course study. In: Journal of Surgical Research. Academic Press Inc.; 2001. p. 104–8.
  • 7. Hasanoğlu Adnan, Erkan Serkan, Temel Selim, Urhan M. Kemal, Güler Osman. Effect of sildenafil citrate on healing of colonic anastomoses. Turkish Medical Journal. 2007;1:66–75.
  • 8. Molyneux G, Gibson FM, Gordon-Smith EC, Pilling AM, Liu KC, Rizzo S, et al. The haemotoxicity of mitomycin in a repeat dose study in the female CD-1 mouse. Vol. 86, Int. J. Exp. Path. 2005.
  • 9. Phillips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H. Effects of Chronic Corticosteroids and Vitamin A on the Healing of Intestinal Anastomoses. The American Journal of Surgery. 1992 Jan;163:71–7.
  • 10. NCCN Clinical practice guidelines in oncology, Colon Cancer Version 1.2022.
  • 11. Schneebaum S, Arnold MW, Staubus A, Young DC, Dumond D, Martin EW. Intraperitoneal Hyperthermic Perfusion with Mitomycin C for Colorectal Cancer with Peritoneal Metastases. Vol. 3, Annals of Surgical Oncology. 1996.
  • 12. López-López V, Lynn PB, Gil J, García-Salom M, Gil E, González A, et al. Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model. Clinical and Translational Oncology. 2019 Apr 9;21(4):505–11.
  • 13. Hasanoğlu Adnan, Erkan Serkan, Temel Selim, Urhan M. Kemal, Güler Osman. Effect of sildenafil citrate on healing of colonic anastomoses. Turkish Medical Journal. 2007;(1):66–75.
  • 14. Cakir T, Ozer I, Bostanci EB, Keklik TT, Ercin U, Bilgihan A, et al. Increased collagen maturity with sildenafil citrate: Experimental high-risk colonic anastomosis model. International Journal of Surgery. 2015 Jan 1;13:152–6.
  • 15. Whealon MD, Gahagan J v., Sujatha-Bhaskar S, O’Leary MP, Selleck M, Dumitra S, et al. Is Fecal Diversion Needed in Pelvic Anastomoses During Hyperthermic Intraperitoneal Chemotherapy (HIPEC)? Ann Surg Oncol. 2017 Aug 1;24(8):2122–8.
  • 16. Piso P, Nedelcut SD, Rau B, Königsrainer A, Glockzin G, Ströhlein MA, et al. Morbidity and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Data from the DGAV StuDoQ Registry with 2149 Consecutive Patients. Ann Surg Oncol. 2019 Jan 15;26(1):148–54.
  • 17. Gorur M, Sozutek A, Irkorucu O, Karakaya B. The influence of platelet-rich plasma (PRP) on colonic anastomosis healing is impaired by intraperitoneal 5-fluorouracil application. An experimental study. Acta Cir Bras. 2020;35(5):1–9.
  • 18. Buk OF, Ocak S, Genc B, Avcı B, Uzuner HO. Is platelet-rich plasma improves the anastomotic healing in hyperthermic intraperitoneal chemotherapy with oxaliplatin: An experimental rat study. Ann Surg Treat Res. 2020;98(2):89–95.
  • 19. Jacquet P. Sugarbaker PH. Abdominal adhesions causing intestinal obstruction following cytoreductive surgery and early postoperative intraperitoneal chemotherapy. Acta Chir Austriaca. 1995;2.
  • 20. Ayten R, Çetinkaya Z, Girgin M, Ozercan I, Ustundag B, Aygen E. The effects of intraperitoneal sildenafil administration on healing of left colonic anastomoses and intra-abdominal adhesion formation in the presence of intra-abdominal infection. Dis Colon Rectum. 2008 Dec;51(12):1837–41.
  • 21. Taş A, Atasoy N, Özbek H, Aslan L, Yüksel H, Ceylan E, et al. The effects of sildenafil citrate (viagra) in the early phase of the healing process in open wounds in dogs. Acta Veterinaria Brno. 2003;72(2):273–7.
  • 22. David A. Zisman, Marvin Schwarz. A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis. New England Journal of Medicine [Internet]. 2010 Aug 12 [cited 2022 May 1];363(7):620–8. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1002110
  • 23. Øines MN, Krarup PM, Jorgensen LN, Ågren MS. Pharmacological interventions for improved colonic anastomotic healing: A meta-analysis. Vol. 20, World Journal of Gastroenterology. WJG Press; 2014. p. 12637–48.
  • 24. Karahasanoğlu T, Altınlı E, Hamzaoğlu İ. Effect of growth hormone treatment on the healing of left colonic anastomoses in protein-malnourished rats. British Journal of Surgery. 1998;85:931–3.
  • 25. Moran M, Ozmen MM, Duzgun AP, Gok R, Renda N, Sedan S, et al. The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: An experimental study. World Journal of Emergency Surgery. 2007;2(1).
  • 26. Dauser B, Heitland W, Bader FG, Brunner W, Nir Y, Zbar AP. Histologic changes in early colonic anastomotic healing using autologous platelet-rich fibrin matrix. European Surgery - Acta Chirurgica Austriaca. 2020 Aug 1;52(4):155–64.
  • 27. Sümer A, Altinli E, Senger S, Köksal N, Onur E, Eroǧlu E, et al. Effect of pentoxifylline and vinpocetine on the healing of ischemic colon anastomosis: An experimental study. Ulusal Travma ve Acil Cerrahi Dergisi. 2011;17(6):482–7.

The protective effect of sildenafil on colon anastomosis in a rat model undergoing hypertermic intraperitoneal chemotherapy

Year 2025, Volume: 35 Issue: 2, 374 - 381, 30.04.2025
https://doi.org/10.54005/geneltip.1476892

Abstract

Aim: The aim of this study was to investigate the effects of sildenafil on colonic anastomosis healing in rats treated with hyperthermic intraperitoneal chemotherapy.
Method: In our study, 30 Wistar-albino rats were used. 30 rats were divided into 3 groups: the sildenafil, control and sham groups. Left colon anastomosis was performed on rats in all three groups.The HIPEC procedure was applied to sildenafil group and control group. During the postoperative period, sildenafil was given orally to the sildenafil group. On the 7th day, the anastomotic loop was excised, and bursting pressure, and adhesion were evaluated. Anastomotic loop was evaluated histopathologically. The results were compared statistically.
Results: When the results were evaluated considering bursting pressure, and adhesion between the sildenafil group and control group, there was no difference. Considering adhesion, the sham group was superior to the other two groups. Histopathological examination reveals that the sham group was significantly superior to the other two groups in terms of anastomototic re-epitelization and muscle separation. There was a significant difference between the sildenafil group and the control group in terms of fibrosis and granulation.
Conclusion: On colon anastomosis performed together with HIPEC application, histopathologically positive effects of sildenafil were observed. The burst pressure of colon anastomosis was not significantly different.

References

  • 1. Bruce J, Krukowski ZH, Al-Khairy G, Russell EM, Park KGM. A systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery. British Journal of Surgery [Internet]. 2001;88:1157–68. Available from: www.bjs.co.uk
  • 2. Moran H, Moran BJ, Heald RJ. Anastomotic Leakage After Colorectal Anastomosis. Vol. 18, Seminars in Surgical Oncology. 2000.
  • 3. Pelz JOW, Doerfer J, Decker M, Dimmler A, Hohenberger W, Meyer T. Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Int J Colorectal Dis. 2007 Aug;22(8):941–7.
  • 4. Turaga K, Levine E, Barone R, Sticca R, Petrelli N, Lambert L, et al. Consensus guidelines from the American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States. Ann Surg Oncol. 2014;21(5):1501–5.
  • 5. Uzun H, Konukoglu D, Nuri MK, Ersoy EY, Özçevik S, Yavuz N. The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: Its relationship between nitric oxide and oxidative stress. World J Surg. 2008 Sep;32(9):2107–13.
  • 6. Lee RH, Efron D, Tantry U, Barbul A. Nitric oxide in the healing wound: A time-course study. In: Journal of Surgical Research. Academic Press Inc.; 2001. p. 104–8.
  • 7. Hasanoğlu Adnan, Erkan Serkan, Temel Selim, Urhan M. Kemal, Güler Osman. Effect of sildenafil citrate on healing of colonic anastomoses. Turkish Medical Journal. 2007;1:66–75.
  • 8. Molyneux G, Gibson FM, Gordon-Smith EC, Pilling AM, Liu KC, Rizzo S, et al. The haemotoxicity of mitomycin in a repeat dose study in the female CD-1 mouse. Vol. 86, Int. J. Exp. Path. 2005.
  • 9. Phillips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H. Effects of Chronic Corticosteroids and Vitamin A on the Healing of Intestinal Anastomoses. The American Journal of Surgery. 1992 Jan;163:71–7.
  • 10. NCCN Clinical practice guidelines in oncology, Colon Cancer Version 1.2022.
  • 11. Schneebaum S, Arnold MW, Staubus A, Young DC, Dumond D, Martin EW. Intraperitoneal Hyperthermic Perfusion with Mitomycin C for Colorectal Cancer with Peritoneal Metastases. Vol. 3, Annals of Surgical Oncology. 1996.
  • 12. López-López V, Lynn PB, Gil J, García-Salom M, Gil E, González A, et al. Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model. Clinical and Translational Oncology. 2019 Apr 9;21(4):505–11.
  • 13. Hasanoğlu Adnan, Erkan Serkan, Temel Selim, Urhan M. Kemal, Güler Osman. Effect of sildenafil citrate on healing of colonic anastomoses. Turkish Medical Journal. 2007;(1):66–75.
  • 14. Cakir T, Ozer I, Bostanci EB, Keklik TT, Ercin U, Bilgihan A, et al. Increased collagen maturity with sildenafil citrate: Experimental high-risk colonic anastomosis model. International Journal of Surgery. 2015 Jan 1;13:152–6.
  • 15. Whealon MD, Gahagan J v., Sujatha-Bhaskar S, O’Leary MP, Selleck M, Dumitra S, et al. Is Fecal Diversion Needed in Pelvic Anastomoses During Hyperthermic Intraperitoneal Chemotherapy (HIPEC)? Ann Surg Oncol. 2017 Aug 1;24(8):2122–8.
  • 16. Piso P, Nedelcut SD, Rau B, Königsrainer A, Glockzin G, Ströhlein MA, et al. Morbidity and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Data from the DGAV StuDoQ Registry with 2149 Consecutive Patients. Ann Surg Oncol. 2019 Jan 15;26(1):148–54.
  • 17. Gorur M, Sozutek A, Irkorucu O, Karakaya B. The influence of platelet-rich plasma (PRP) on colonic anastomosis healing is impaired by intraperitoneal 5-fluorouracil application. An experimental study. Acta Cir Bras. 2020;35(5):1–9.
  • 18. Buk OF, Ocak S, Genc B, Avcı B, Uzuner HO. Is platelet-rich plasma improves the anastomotic healing in hyperthermic intraperitoneal chemotherapy with oxaliplatin: An experimental rat study. Ann Surg Treat Res. 2020;98(2):89–95.
  • 19. Jacquet P. Sugarbaker PH. Abdominal adhesions causing intestinal obstruction following cytoreductive surgery and early postoperative intraperitoneal chemotherapy. Acta Chir Austriaca. 1995;2.
  • 20. Ayten R, Çetinkaya Z, Girgin M, Ozercan I, Ustundag B, Aygen E. The effects of intraperitoneal sildenafil administration on healing of left colonic anastomoses and intra-abdominal adhesion formation in the presence of intra-abdominal infection. Dis Colon Rectum. 2008 Dec;51(12):1837–41.
  • 21. Taş A, Atasoy N, Özbek H, Aslan L, Yüksel H, Ceylan E, et al. The effects of sildenafil citrate (viagra) in the early phase of the healing process in open wounds in dogs. Acta Veterinaria Brno. 2003;72(2):273–7.
  • 22. David A. Zisman, Marvin Schwarz. A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis. New England Journal of Medicine [Internet]. 2010 Aug 12 [cited 2022 May 1];363(7):620–8. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1002110
  • 23. Øines MN, Krarup PM, Jorgensen LN, Ågren MS. Pharmacological interventions for improved colonic anastomotic healing: A meta-analysis. Vol. 20, World Journal of Gastroenterology. WJG Press; 2014. p. 12637–48.
  • 24. Karahasanoğlu T, Altınlı E, Hamzaoğlu İ. Effect of growth hormone treatment on the healing of left colonic anastomoses in protein-malnourished rats. British Journal of Surgery. 1998;85:931–3.
  • 25. Moran M, Ozmen MM, Duzgun AP, Gok R, Renda N, Sedan S, et al. The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: An experimental study. World Journal of Emergency Surgery. 2007;2(1).
  • 26. Dauser B, Heitland W, Bader FG, Brunner W, Nir Y, Zbar AP. Histologic changes in early colonic anastomotic healing using autologous platelet-rich fibrin matrix. European Surgery - Acta Chirurgica Austriaca. 2020 Aug 1;52(4):155–64.
  • 27. Sümer A, Altinli E, Senger S, Köksal N, Onur E, Eroǧlu E, et al. Effect of pentoxifylline and vinpocetine on the healing of ischemic colon anastomosis: An experimental study. Ulusal Travma ve Acil Cerrahi Dergisi. 2011;17(6):482–7.
There are 27 citations in total.

Details

Primary Language English
Subjects Gastroenterology and Hepatology
Journal Section Original Article
Authors

Ahmet Başak 0000-0001-7308-010X

Mehmet Timuçin Aydın 0000-0003-2835-5308

Mehmet Mahir Fersahoğlu 0000-0003-2526-1832

İksan Taşdelen 0000-0001-9289-2744

Adnan Somay 0000-0002-7399-4873

Emre Teke 0000-0001-7597-6401

Erdem Durum 0000-0002-8766-9035

Kemal Memişoğlu 0000-0002-9486-4648

Publication Date April 30, 2025
Submission Date May 4, 2024
Acceptance Date April 15, 2025
Published in Issue Year 2025 Volume: 35 Issue: 2

Cite

Vancouver Başak A, Aydın MT, Fersahoğlu MM, Taşdelen İ, Somay A, Teke E, Durum E, Memişoğlu K. The protective effect of sildenafil on colon anastomosis in a rat model undergoing hypertermic intraperitoneal chemotherapy. Genel Tıp Derg. 2025;35(2):374-81.

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