Skip to main content

Advertisement

Log in

The Effects of Adjuvant Experimental Radioimmunotherapy and Hyperthermic Intraperitoneal Chemotherapy on Intestinal and Abdominal Healing after Cytoreductive Surgery for Peritoneal Carcinomatosis in the Rat

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined.

Methods

PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq 177lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery.

Results

At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter.

Conclusion

As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Esquivel J, Sticca R, Sugarbaker P, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Ann Surg Oncol 2007; 14:128–33

    PubMed  CAS  Google Scholar 

  2. Kusamura S, Younan R, Baratti D, et al. Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer 2006; 106:1144–53

    Article  PubMed  Google Scholar 

  3. Younan R, Kusamura S, Baratti D, et al. Bowel complications in 203 cases of peritoneal surface malignancies treated with peritonectomy and closed-technique intraperitoneal hyperthermic perfusion. Ann Surg Oncol 2005; 12:910–8

    Article  PubMed  Google Scholar 

  4. Elias D, Blot F, El OA, et al. Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy. Cancer 2001; 92:71–6

    Article  PubMed  CAS  Google Scholar 

  5. Culliford AT, Brooks AD, Sharma S, et al. Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer. Ann Surg Oncol 2001; 8:787–95

    Article  PubMed  Google Scholar 

  6. Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004; 22:3284–92

    Article  PubMed  CAS  Google Scholar 

  7. Glehen O, Cotte E, Schreiber V, et al. Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin. Br J Surg 2004; 91:747–54

    Article  PubMed  CAS  Google Scholar 

  8. Koppe MJ, Hendriks T, Boerman OC, et al. Radioimmunotherapy is an effective adjuvant treatment modality after cytoreductive surgery of peritoneal carcinomatosis of colonic origin. J Nucl Med 2006; 47:1867–74

    PubMed  CAS  Google Scholar 

  9. Aarts F, Koppe MJ, Hendriks T, et al. Timing of adjuvant radioimmunotherapy after cytoreductive surgery in experimental peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 2007; 14:533–40

    Article  PubMed  Google Scholar 

  10. Aarts F, Hendriks T, Boerman OC, et al. A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats. Ann Surg Oncol 2007; 14:3274–82

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. Zedeck MS. A model system for studies of colon carcinogenesis: tumor induction by a single injection of methylazoxymethanol acetate. J Natl Cancer Inst 1974; 53:1419–21

    PubMed  CAS  Google Scholar 

  13. Hagenaars M, Koelemij R, Ensink NG, et al. The development of novel mouse monoclonal antibodies against the CC531 rat colon adenocarcinoma. Clin Exp Metastasis 2000; 18:281–9

    Article  PubMed  CAS  Google Scholar 

  14. Verhofstad MH, Hendriks T. Complete prevention of impaired anastomotic healing in diabetic rats requires preoperative blood glucose control. Br J Surg 1996; 83:1717–21

    Article  PubMed  CAS  Google Scholar 

  15. de Hingh I, Lomme RM, van GH, et al. Changes in gelatinase activity in the gastrointestinal tract after anastomotic construction in the ileum or colon. Dis Colon Rectum 2005; 48:2133–41

    Article  PubMed  Google Scholar 

  16. Jacquet P, Stephens AD, Averbach AM, et al. Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer 1996; 77:2622–9

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique. Ann Surg Oncol 1999; 6:790–6

    Article  PubMed  CAS  Google Scholar 

  19. Verwaal VJ, van TH, Ruth SV, et al. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol 2004; 85:61–7

    Article  PubMed  Google Scholar 

  20. Bozer M, Turkcapar N, Bayar S, et al. Intraperitoneal hyperthermic perfusion may induce bacterial translocation. Hepatogastroenterology 2005; 52:111–4

    PubMed  Google Scholar 

  21. van der Kolk BM, de Man BM, Wobbes T, et al. Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine? Br J Cancer 1999; 79:545–50

    Article  PubMed  Google Scholar 

  22. 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

    Article  PubMed  Google Scholar 

  23. Makrin V, Lev-Chelouche D, Even SE, et al. Intraperitoneal heated chemotherapy affects healing of experimental colonic anastomosis: an animal study. J Surg Oncol 2005; 89:18–22

    Article  PubMed  CAS  Google Scholar 

  24. Seifert WF, Biert J, Wobbes T, et al. Late effects of intraoperative radiation therapy in anastomotic rat colon. Int J Radiat Oncol Biol Phys 1998; 42:623–9

    PubMed  CAS  Google Scholar 

  25. Strup-Perrot C, Vozenin-Brotons MC, Vandamme M, et al. Expression and activation of MMP -2, -3, -9, -14 are induced in rat colon after abdominal X-irradiation. Scand J Gastroenterol 2006; 41:60–70

    Article  PubMed  CAS  Google Scholar 

  26. Dams ET, Reijnen MM, Oyen WJ, et al. Imaging experimental intraabdominal abscesses with 99 mTc-PEG liposomes and 99 mTc-HYNIC IgG. Ann Surg 1999; 229:551–7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Henny Eikholt, Maarten Brom, and Bianca Lemmers (Radboud University Nijmegen Medical Center, Central Animal Laboratory) for their assistance in the animal experiments and Annemarie Eek for the excellent assistance on radiolabeling procedures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Aarts MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aarts, F., Bleichrodt, R.P., 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 15, 3299–3307 (2008). https://doi.org/10.1245/s10434-008-0070-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-008-0070-4

Keywords

Navigation