Skip to main content

Advertisement

Log in

Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Aim

The aim of this experimental study was to investigate the effect of intraperitoneal administration of oxaliplatin on the healing of colonic anastomoses when injected immediately after colon resection.

Materials and methods

Thirty male Wistar rats were used. During the operation, the rats were randomized to two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or oxaliplatin (2.4 mg/kg body weight) depending on their group. All rats were killed on the eighth postoperative day. The anastomoses were examined macroscopically. The anastomotic bursting pressures were recorded, the anastomoses graded histologically, and the hydroxyproline tissue contents determined.

Results

Anastomotic leakage was noted in four rats (26.7%) of the oxaliplatin group, whereas no anastomotic dehiscence was detected among rats of the control group (p = 0.016). The adhesion formation at the anastomotic sites and the inflammatory cell infiltration were significantly higher in the oxaliplatin group than in the control group (p = 0.001). The bursting pressures (p = 0.001), the hydroxyproline tissue content (p = 0.001), the neoangiogenesis (p = 0.033), the fibroblast activity (p = 0.001), and the collagen deposition (p = 0.001) were significantly lower in the oxaliplatin group in comparison to the control group.

Conclusion

The immediate postoperative intraperitoneal administration of oxaliplatin seems to impair healing of colonic anastomoses in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kanellos I, Blouhos K, Demetriades H, Pramateftakis MG, Mantzoros I, Zacharakis E, Betsis D (2004) The failed intraperitoneal colon anastomosis after colon resection. Tech Coloproctology 8:53–56

    Article  Google Scholar 

  2. Mann B, Kleinschmidt S, Stremmel W (1996) Prospective study of hand-sutured anastomosis after colorectal resection. Br J Surg 83:29–34

    Article  PubMed  CAS  Google Scholar 

  3. Golub R, Golub RW, Cantu R Jr, Stein HD (1997) A multivariate analysis of factors contributing to leakage of intestinal anastomoses. J Am Coll Surg 184:364–369

    PubMed  CAS  Google Scholar 

  4. Kanellos I, Zacharakis E, Christoforidis E, Demetriades H, Betsis D (2002) Low anterior resection without protective colostomy. Tech Coloproctology 6:153–156

    Article  CAS  Google Scholar 

  5. Vailant JC, Nordlinger B, Deuffic S, Arnaud JP, Pelissier E, Favre JP, Jaeck D, Fourtanier G, Grandjean JP, Marre P, Letoublon C (2000) Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: a multicenter phase III trial. Ann Surg 231:449–452

    Article  Google Scholar 

  6. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, Francois Y, Vignal J, Gilly FN (2000) Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 88:364–368

    Article  Google Scholar 

  7. Martens MF, Hendriks T, Wobbes T, De Pont JJ (1992) Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomoses. Br J Cancer 65:649–653

    PubMed  CAS  Google Scholar 

  8. Hananel N, Gordon PH (1995) Effect of 5-flouopouracil and leucovorin on the integrity of colonic anastomoses in the rat. Dis Colon Rectum 38:886–890

    Article  PubMed  CAS  Google Scholar 

  9. Bostanoglu S, Dincer S, Keskin A, Bostanoglu A, Dursun A, Serim C (1998) Beneficial effect of Iloprost on impaired wound healing induced by intraperitoneal 5-flouorouracil infusion. Dis Colon Rectum 41:642–646

    Article  PubMed  CAS  Google Scholar 

  10. Kanellos I, Odisseos C, Zaramboukas T, Kavouni A, Galovatsea K, Dadoukis I (1997) Colonic healing after early intraperitoneal administration of 5-flouorouracil and interferon in rats. Int J Colorectal Dis 12:45–49

    Article  PubMed  CAS  Google Scholar 

  11. Kanellos I, Kavouni A, Zaraboukas T, Odisseos C, Galovatsea K, Dadoukis I (1996) Influence of intraperitoneal 5-flouorouracil plus folinic acid on the healing of colonic anastomoses in rats. Eur Surg Res 28:374–378

    Article  PubMed  CAS  Google Scholar 

  12. Kanellos I, Mantzoros I, Demetriades H, Kalfadis S, Kelpis T, Sakkas L, Betsis D (2004) Healing of colon anastomosis covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-flouorouracil. Dis Colon Rectum 47:510–514

    Article  PubMed  CAS  Google Scholar 

  13. Scartozzi M, Sobrero A, Gasparini G, Berardi R, Catalano V, Graziano F, Barni S, Zaniboni A, Beretta GD, Ladianca R, Cascinu S (2005) The role of 5-fluoroucacil (5-FU) reintroduction with irinotecan or oxaliplatin in truly 5-FU-refractory advanced colorectal cancer patients. Oncology 68:212–216

    Article  PubMed  CAS  Google Scholar 

  14. Pestieau SR, Belliveau JF, Griffin H, Stuart OA (2001) Pharmacokinetics of intraperitoneal oxaliplatin: experimental studies. J Surg Oncol 76:106–114

    Article  PubMed  CAS  Google Scholar 

  15. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B (2004) Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15:460–466

    Article  PubMed  CAS  Google Scholar 

  16. Van der Hamm A, Kort W, Weijma I, Van Der Ingh H, Jeekel H (1992) Effect of antobiotics in fibrin sealant on healing colonic anastomosis in the rat. Br J Surg 74:525–528

    Google Scholar 

  17. Philips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H (1992) Effects of chronic corticosteroid and vitamin A on the healing of intestinal anastomoses. Am J Surg 163:71–77

    Article  Google Scholar 

  18. Reddy GK, Enweneka CS (1996) A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 29:225–229

    Article  PubMed  CAS  Google Scholar 

  19. Villar JM, Martinez AP, Villegas MT, Muffak K, Mansilla A, Garrote D, Ferron JA (2005) Surgical options for malignant left-sided colonic obstruction. Surg Today 35:275–281

    Article  PubMed  Google Scholar 

  20. Amoruso M, D’Abbicco D, Notarnicola A, Angrisano A, Nacchiero M, Martino Bonomo G (2001) Early colorectal reoperation: risk factors. Chir Ital 53:827–833

    PubMed  CAS  Google Scholar 

  21. Buchmiller-Crair TL, Kim CS, Won NH, Chopourian HL, Shaw KS, Fonkalsrud EW (2000) Effect of acute anemia on the healing of intestinal anastomoses in the rabbit. J Trauma 51:363–368

    Article  Google Scholar 

  22. Graf W, Westlin JE, Pahlman L, Glimelius B (1994) Adjuvant intraperitoneal 5-flouorouracil and intravenous leucovorin after colorectal cancer surgery. A randomized phase II placebo-controlled study. Int J Colorectal Dis 9:35–39

    Article  PubMed  CAS  Google Scholar 

  23. Graf W, Weiber S, Glimelious B, Jiborn H, Pahlman L, Zederfeldt B (1992) Influence of 5-flouorouracil and folinic acid on colonic healing: an experimental study in the rat. Br J Surg 79:825–830

    Article  PubMed  CAS  Google Scholar 

  24. Mathe G, Kidani Y, Triana K (1986) A phase I trial of trans-1-diaminocyclohexane oxalo-platinum (L-OHP). Bio-med Pharmacother 40:372–376

    CAS  Google Scholar 

  25. Raymond E, Chaney SG, Taamma A (1998) Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 9:1053–1071

    Article  PubMed  CAS  Google Scholar 

  26. Hribaschek A, Pross M, Kuhn R, Kruger S, Ridwelski K, Halangk W, Boltze C, Lippert H (2002) Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin. Anti-Cancer Drugs 13:605–614

    Article  PubMed  CAS  Google Scholar 

  27. Elias D, Sideris L, Pocard M, Ede C, Ben Hassouna D, Ducreux M, Boige V, Cote JF, Lasser P (2004) Efficacy of intraperitoneal chemohyperthermia with oxaliplatin in colorectal peritoneal carcinomatosis. Preliminary results in 24 patients. Ann Oncol 15:781–785

    Article  PubMed  CAS  Google Scholar 

  28. Cihan A, Armutcu F, Ucan BH, Acun Z, Numanoglu VK, Gurel A, Ulukent SC (2003) Comparison of the measurement methods of bursting pressure of intestinal anastomoses. Hepatogastroenterology 50:232–234

    Google Scholar 

  29. Pramateftakis M-G, Kanellos D, Demetriades H, Kanellos I, Mantzoros I, Zacharakis E, Despoudi K, Angelopoulos S, Koliakos G, Zaraboukas T, Betsis D (2007) The effects of irinotecan on the healing of colonic anastomoses in rats. O J Surg 1:1–6

    CAS  Google Scholar 

  30. Vasiliadis K, Pramateftakis MG, Blouhos K, Mantzoros I, Koliakos G, Zaraboukas T, Kanellos I, Demetriades H, Alamdari DH, Betsis D (2007) Effect of iloprost on impaired anastomotic healing caused by 5-fluorouracil plus leucovorin. Dis Colon Rectum 50:899–907

    Article  PubMed  CAS  Google Scholar 

  31. Steed DL (2003) Wound-healing trajectories. Surg Clin North Am 83:547–555

    Article  PubMed  Google Scholar 

  32. Brunner G (2003) Theme tissue: wound healing mechanisms. Thromb Haemost 90:976–977

    PubMed  CAS  Google Scholar 

  33. Rabinovsky ED, Draghia-Akli R (2004) Insulin-like growth factor I plasmid therapy promotes in vivo angiogenesis. Mol Ther 9:46–55

    Article  PubMed  CAS  Google Scholar 

  34. Bulstrode NW, Mudera V, McGrouther DA, Grobbelaar AO, Cambrey AD (2005) 5-Fluorouracil selectively inhibits collagen synthesis. Plast Reconstr Surg 116:209–221

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ioannis Kanellos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanellos, D., Pramateftakis, MG., Demetriades, H. et al. Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin. Int J Colorectal Dis 23, 1185–1191 (2008). https://doi.org/10.1007/s00384-008-0538-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-008-0538-5

Keywords

Navigation