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Clinical and Translational Oncology

, Volume 21, Issue 4, pp 505–511 | Cite as

Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model

  • V. López-LópezEmail author
  • P. B. Lynn
  • J. Gil
  • M. García-Salom
  • E. Gil
  • A. González
  • I. P. Muñoz
  • P. A. Cascales-Campos
Research Article

Abstract

Background

Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model.

Methods

After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals’ peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically.

Results

Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups).

Conclusion

Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

Keywords

Paclitaxel Hyperthermic Intraperitoneal Chemotherapy Colonic anastomoses Healing 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declared no conflict of interest. No third-party financial funds or materials were accepted or necessary for the execution of this research project.

Research involving human participants and/or animals

Maintenance and care of all the animals included were according with national directives from the Protection commission and National Institute of health for laboratory animal.

Informed consent

The research did not involve human participants.

References

  1. 1.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.CrossRefGoogle Scholar
  2. 2.
    Smeenk RM, Verwaal VJ, Zoetmulder FA. Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei—a report of 103 procedures. Eur J Surg Oncol. 2006;32:186–90.CrossRefGoogle Scholar
  3. 3.
    Nesbakken A, Nygaard K, Lunde OC, et al. Anastomotic leak following mesorectal excision for rectal cancer: true incidence and diagnostic challenges. Colorectal Dis. 2005;7:576–81.CrossRefGoogle Scholar
  4. 4.
    Frasson M, Flor-Lorente B, Rodríguez JL, et al. Risk factors for anastomotic leak after colon resection for cancer: multivariate analysis and nomogram from a multicentric, prospective, national study with 3193 patients. Ann Surg. 2015;262:321–30.CrossRefGoogle Scholar
  5. 5.
    Pelz JO, Doerfer J, Decker M, et al. Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Int J Colorectal Dis. 2007;22:941–7.CrossRefGoogle Scholar
  6. 6.
    Khoury GA, Waxman BP. Large bowel anastomosis. I. The healing process and sutured anastomosis. A review. Br J Surg. 1983;70:61–3.CrossRefGoogle Scholar
  7. 7.
    Fumagalli U, Trabucchi E, Soligo M, et al. Effects of intraperitoneal chemotherapy on anastomotic healing in rats. J Surg Res. 1991;50:82–7.CrossRefGoogle Scholar
  8. 8.
    Makrin V, Lev-Chelouche D, Even Sapir E, et al. Intraperitoneal heated chemotherapy affects healing of experimental colonic anastomosis: an animal study. J Surg Oncol. 2005;89:18–22.CrossRefGoogle Scholar
  9. 9.
    Wagner OJ, Inglin RA, Bisch-knaden S, et al. Sirolimus and intraoperative hyperthermic peritoneal chemoperfusion with mitomycin-C do not impair healing of bowel anastomoses. Transpl Int. 2008;21:554–63.CrossRefGoogle Scholar
  10. 10.
    Arikan AY, Günal O, Pehlivan M, et al. The effect of intraperitoneal paclitaxel administration on colonic anastomosis. Hepatogastroenterology. 2000;47:1273–6.Google Scholar
  11. 11.
    Uzunkoy A, Bolukbas C, Horoz M, et al. The optimal starting time of postoperative intraperitoneal mitomycin-C therapy with preserved intestinal wound healing. BMC Cancer. 2005;5:31.CrossRefGoogle Scholar
  12. 12.
    Kanellos I, Mantzoros I, Demetriades H, et al. Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil. Dis Colon Rectum. 2004;47:510–5.CrossRefGoogle Scholar
  13. 13.
    Kuzu M, Koksoy C, Kale T, et al. Experimental study of the effect of preoperative 5-fluorouracil on the integrity of colonic anastomoses. Br J Surg. 1985;85:236–9.CrossRefGoogle Scholar
  14. 14.
    Kanellos D, Pramateftakis MG, Demetriades H, et al. Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin. Int J Colorectal Dis. 2008;23:1185–91.CrossRefGoogle Scholar
  15. 15.
    Morrison JP, Coleman MC, Aunan ES, et al. Aging reduces responsiveness to BSO- and heat stress-induced perturbations of glutathione and antioxidant enzymes. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1035–41.CrossRefGoogle Scholar
  16. 16.
    Cui Y, Liu B, Xie J, et al. Effect of heat stress and recovery on viability, oxidative damage, and heat shock protein expression in hepatic cells of grass carp (Ctenopharyngodon idellus). Fish Physiol Biochem. 2013;40:721–9.CrossRefGoogle Scholar
  17. 17.
    Oliver SR, Philips NA, Novosad VL, et al. Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism. Am J Physiol Regul Integr Comp Physiol. 2012;302:R845–53.CrossRefGoogle Scholar
  18. 18.
    Pelz JO, Vetteriein M, Grimming T, et al. Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and dissecting effects of hyperthermia. Ann Surg Oncol. 2013;20:1105–13.CrossRefGoogle Scholar
  19. 19.
    Altup S, Demiryürek AT, Ak D, et al. Contribution of peroxynitrite to the beneficial effects of preconditioning on ischaemia-induced arrhythmias in rat isolated hearts. Eur J Pharmacol. 2001;415:239–46.CrossRefGoogle Scholar
  20. 20.
    Csonka C, Csont Onody A, et al. Preconditioning decreases ischemia/reperfusion-induced peroxynitrite formation. Biochem Biophys Res Commun. 2001;285:1217–9.CrossRefGoogle Scholar
  21. 21.
    Cascales Campos P, Gil J, Parrilla P. Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with primary and recurrent advanced ovarian cancer. Eur J Surg Oncol. 2014;40:970–5.CrossRefGoogle Scholar
  22. 22.
    BOE.es [Internet]. Spain: agencia estatal boletín oficial del estado. Available at: http://boe.es/buscar/doc.php?id=BOE-A-2005-17344. Accessed 25 Oct 2005.
  23. 23.
    Farriol M, Rosselló J, Schwartz S. Body Surface area in Sprague-Dawley rats. J Anim Physiol Anim Nutr (Berl). 1997;77:61–5.CrossRefGoogle Scholar
  24. 24.
    Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother. 2013;4:303–6.CrossRefGoogle Scholar
  25. 25.
    Aarts F, Blechrodt RP, de Man B, et al. The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat. Ann Surg Oncol. 2008;15:3299–307.CrossRefGoogle Scholar
  26. 26.
    Marjanovic G, Jüttner E, zur Hausen A, et al. Ischemic preconditioning improves stability of intestinal anastomoses in rats. Int J Colorectal Dis. 2009;24:975–81.CrossRefGoogle Scholar
  27. 27.
    Zacharakis E, Demetriades H, Kanellos D, et al. Contribution of insulin-like growth factor I to the healing of colonic anastomoses in rats. J Invest Surg. 2007;20:9–14.CrossRefGoogle Scholar
  28. 28.
    Makrin V, Lev-Chelouche D, Even Sapir E, et al. Intraperitoneal heated chemotherapy affects healing of experimental colonic anastomosis: an animal study. J Surg Oncol. 2005;89:18–22.CrossRefGoogle Scholar
  29. 29.
    Yüceyar S, Ertürk S, Temiz M, et al. Role of the antiangiogenetic drug paclitaxel on healing of intestinal anastomosis: an experimental study. Tech Coloproctol. 2005;9:201–5.CrossRefGoogle Scholar
  30. 30.
    Shimizu T, Maeta M, Koga S. Influence of local hyperthermia on the healing of small intestinal anastomoses in the rat. Br J Surg. 1991;78:57–9.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Virgen de la Arrixaca Clinic and University Hospital, General Surgery, IMIBMurciaSpain
  2. 2.Surgery DepartmentNew York University School of MedicineNew YorkUSA
  3. 3.Gerencia del Area de Salud III (Lorca)MurciaSpain
  4. 4.Hospital Virgen del Castillo (Yecla)MurciaSpain

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