Skip to main content

Advertisement

SpringerLink
Log in

Prevention of Peritoneal Carcinomatosis from Colon Cancer Cell Seeding Using a Pirarubicin Solution in Rats and Nude Mice

  • Original Scientific Reports
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

ABSTRACT

Free malignant cells, which are frequently detected in the washing liquid from the peritoneal cavity before and after resection of human colorectal cancer, are suspected to cause recurrent peritoneal cancer. We carried out an experimental study to compare the prophylactic efficacy of washing the peritoneum with several anticancer drugs and the antiseptic povidone-iodine against the development of peritoneal carcinomatosis from colonic origin in rats and nude mice. The in vitro anticancer activity of a short, 15-minute exposure of pirarubicin, doxorubicin, 5-fluorouracil, cisplatin, mitomycin C, and 1% povidone-iodine was first evaluated by an MTT assay on DHD/K12/PROb rat and LS174T human colon cancer cells. For the in vivo experiments, BDIX rats were inoculated intraperitoneally (IP) with 1 x 106 DHD/K12/PROb cells followed by peritoneal scarring and a colocolic anastomosis. A 15-minute peritoneal washing with the anticancer drugs or povidone-iodine was then performed. Nude mice were IP-inoculated with 1 × 107 LS174T human cells and treated 2 hours later with IP pirarubicin. Only pirarubicin, mitomycin C, and povidone-iodine were fully cytotoxic in vitro against DHD/K12/PROb rat colon cancer cells. In contrast to pirarubicin and povidone-iodine, mitomycin C was not completely active against LS174Tcells. In vivo, pirarubicin cured DHD/K12/PROb-inoculated rats, even at the site of the peritoneal scarring and intestinal anastomosis. IP pirarubicin prevented the development of peritoneal carcinomatosis and liver metastasis in LS174T-inoculated mice. IP washing with pirarubicin cured 2-day-old, but not 7-day-old, peritoneal carcinomatosis in rats. Short exposure to IP pirarubicin is nontoxic and more active than povidone-iodine and other anticancer drugs in preventing the development of peritoneal carcinomatosis from colonic origin in rats and mice. The prophylactic effect of preoperative peritoneal washing with pirarubicin on the development of recurrent peritoneal cancer should be evaluated in a randomized clinical trial.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

References

  1. PH Sugarbaker WJ Cunliffe J Belliveau et al. (1989) ArticleTitleRationale for integrating early postoperative intraperitoneal chemotherapy into the surgical treatment of gastrointestinal cancer Semin. Oncol. 16 83–97 Occurrence Handle1:STN:280:BiaA2cnnvVE%3D Occurrence Handle2669141

    CAS  PubMed  Google Scholar 

  2. HC Umpleby B Fermor MO Symes et al. (1984) ArticleTitleViability of exfoliated colorectal carcinoma cells Br. J. Surg. 71 659–663 Occurrence Handle1:STN:280:BiqD3c7gvVU%3D Occurrence Handle6478151

    CAS  PubMed  Google Scholar 

  3. H Zirngibl B Husemann P Hermanek (1990) ArticleTitleIntraoperative spillage of tumor cells in surgery for rectal cancer Dis. Colon Rectum 33 610–614 Occurrence Handle1:STN:280:By%2BB1MfnsVU%3D Occurrence Handle2361432

    CAS  PubMed  Google Scholar 

  4. AJ Leather G Kocjan F Savage et al. (1994) ArticleTitleDetection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer Dis. Colon Rectum 37 814–819 Occurrence Handle1:STN:280:ByuA3szgvVc%3D Occurrence Handle8055727

    CAS  PubMed  Google Scholar 

  5. LS Wong AG Morris IA Fraser (1996) ArticleTitleThe exfoliation of free malignant cells in the peritoneal cavity during resection of colorectal cancer Surg. Oncol. 5 115–121 Occurrence Handle1:STN:280:ByiD28rhs10%3D Occurrence Handle8908716

    CAS  PubMed  Google Scholar 

  6. K Hase H Ueno N Kuranaga et al. (1998) ArticleTitleIntraperitoneal exfoliated cancer cells in patients with colorectal cancer Dis. Colon Rectum 41 1134–1140 Occurrence Handle1:STN:280:DyaK1cvhvF2htA%3D%3D Occurrence Handle9749497

    CAS  PubMed  Google Scholar 

  7. U Guller P Zajac A Schnider et al. (2002) ArticleTitleDisseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer Ann. Surg. 236 768–775 Occurrence Handle10.1097/00000658-200212000-00009 Occurrence Handle12454515

    Article  PubMed  Google Scholar 

  8. S Aoki Y Takagi M Hayakawa et al. (2002) ArticleTitleDetection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients J. Exp. Clin. Cancer Res. 21 555–562 Occurrence Handle1:CAS:528:DC%2BD3sXitVCmtLk%3D Occurrence Handle12636102

    CAS  PubMed  Google Scholar 

  9. JT Brodsky AM Cohen (1991) ArticleTitlePeritoneal seeding following potentially curative resection of colonic carcinoma: implications for adjuvant therapy Dis. Colon Rectum 34 723–727 Occurrence Handle1:STN:280:By6A3cbkslQ%3D Occurrence Handle1855433

    CAS  PubMed  Google Scholar 

  10. PH Sugarbaker (2002) ArticleTitleNew responsibilities in the management of colorectal cancer with peritoneal seeding Cancer Invest. 20 1118–1122 Occurrence Handle10.1081/CNV-120005929 Occurrence Handle12449746

    Article  PubMed  Google Scholar 

  11. RB Turnbull SuffixJr K Kyle FR Watson et al. (1967) ArticleTitleCancer of the colon: the influence of the no-touch isolation technic on survival rates Ann. Surg. 166 420–427 Occurrence Handle6039601

    PubMed  Google Scholar 

  12. E Hansen N Wolff R Knuechel et al. (1995) ArticleTitleTumor cells in blood shed from the surgical field Arch. Surg. 130 387–393 Occurrence Handle1:STN:280:ByqB38rnt1I%3D Occurrence Handle7710337

    CAS  PubMed  Google Scholar 

  13. P Gertsch HU Baer R Kraft et al. (1992) ArticleTitleMalignant cells are collected on circular staplers Dis. Colon Rectum 35 238–241 Occurrence Handle1:STN:280:By2C2MvpvFM%3D Occurrence Handle1740068

    CAS  PubMed  Google Scholar 

  14. P Jacquet OA Stuart R Dalton et al. (1996) ArticleTitleEffect of intraperitoneal chemotherapy and fibrinolytic therapy on tumor implantation in wound sites J. Surg. Oncol. 62 128–134 Occurrence Handle10.1002/(SICI)1096-9098(199606)62:2<128::AID-JSO9>3.0.CO;2-A Occurrence Handle1:CAS:528:DyaK28XksFSis7k%3D Occurrence Handle8649039

    Article  CAS  PubMed  Google Scholar 

  15. PH Sugarbaker (1991) ArticleTitleMechanisms of relapse for colorectal cancer: implications for intraperitoneal chemotherapy J. Surg. Oncol. 2 36–41 Occurrence Handle1:STN:280:By6A28bktlc%3D

    CAS  Google Scholar 

  16. AM Eggermont EP Steller PH Sugarbaker (1987) ArticleTitleLaparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells Surgery 102 71–78 Occurrence Handle1:STN:280:BiiB3svptVI%3D Occurrence Handle3495896

    CAS  PubMed  Google Scholar 

  17. A Schott I Vogel U Krueger et al. (1998) ArticleTitleIsolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker Ann. Surg. 227 372–379 Occurrence Handle10.1097/00000658-199803000-00009 Occurrence Handle1:STN:280:DyaK1c7os1aruw%3D%3D Occurrence Handle9527060

    Article  CAS  PubMed  Google Scholar 

  18. C Penna B Nordlinger (1996) ArticleTitleLocoregional chemotherapy for adjuvant treatment of colorectal adenocarcinoma Eur. J. Cancer 32 1117–1122 Occurrence Handle10.1016/0959-8049(96)00044-5

    Article  Google Scholar 

  19. W Scheithauer GV Kornek A Marczell et al. (1998) ArticleTitleCombined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma Br. J. Cancer 77 1349–1354 Occurrence Handle1:CAS:528:DyaK1cXislChsbo%3D Occurrence Handle9579845

    CAS  PubMed  Google Scholar 

  20. A Hribaschek R Kuhn M Pross et al. (2001) ArticleTitleProphylaxis of peritoneal carcinomatosis in experimental investigations Int. J. Colorectal Dis. 16 340–345 Occurrence Handle10.1007/s003840100321 Occurrence Handle1:STN:280:DC%2BD3MnhtFyltw%3D%3D Occurrence Handle11686534

    Article  CAS  PubMed  Google Scholar 

  21. G Basha M Ghirardi K Geboes et al. (2000) ArticleTitleLimitations of peritoneal washing with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding: experimental study in rats Dis. Colon Rectum 43 1713–1718 Occurrence Handle1:STN:280:DC%2BD3M%2FpvFGqtg%3D%3D Occurrence Handle11156456

    CAS  PubMed  Google Scholar 

  22. SW Lee NR Gleason M Bessler et al. (1999) ArticleTitlePeritoneal irrigation with povidone-iodine solution after laparoscopic-assisted splenectomy significantly decreases port-tumor recurrence in a murine model Dis. Colon Rectum 42 319–326 Occurrence Handle1:STN:280:DyaK1M3jvValtA%3D%3D Occurrence Handle10223750

    CAS  PubMed  Google Scholar 

  23. CA Jacobi FJ Peter FA Wenger et al. (1999) ArticleTitleNew therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat Dig. Surg. 16 393–399 Occurrence Handle10.1159/000018754 Occurrence Handle1:STN:280:DC%2BD3c%2Fjs12rug%3D%3D Occurrence Handle10567800

    Article  CAS  PubMed  Google Scholar 

  24. SJ Neuhaus DI Watson T Ellis et al. (1999) ArticleTitleInfluence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy Dis. Colon Rectum 42 10–15 Occurrence Handle1:STN:280:DyaK1M3is1CqtA%3D%3D Occurrence Handle10211514

    CAS  PubMed  Google Scholar 

  25. F Martin A Caignard JF Jeannin et al. (1983) ArticleTitleSelection by trypsin of two sublines of rat colon cancer cells forming progressive or regressive tumors Int. J. Cancer 32 623–627 Occurrence Handle1:STN:280:BiuD28%2FjvFI%3D Occurrence Handle6358055

    CAS  PubMed  Google Scholar 

  26. B Chauffert MT Dimanche-Boitrel P Genne et al. (1992) ArticleTitleExperimental chemotherapy of peritoneal carcinomatosis of colonic origin in rats Gastroenterol. Clin. Biol. 16 215–219 Occurrence Handle1:STN:280:By2B2MfmsFU%3D Occurrence Handle1582536

    CAS  PubMed  Google Scholar 

  27. HC Kuijpers (1985) ArticleTitleIs prophylactic abdominal irrigation with polyvinyl pyrrolidone iodine (PVPI) safe? Dis. Colon Rectum 28 481–483 Occurrence Handle1:STN:280:BiqB2MnotFU%3D Occurrence Handle4017806

    CAS  PubMed  Google Scholar 

  28. PH Sugarbaker (1996) ArticleTitleEarly postoperative intraperitoneal Adriamycin as an adjuvant treatment for visceral and retroperitoneal sarcoma Cancer Treat. Res. 81 7–14 Occurrence Handle1:STN:280:BymH3s7kvV0%3D Occurrence Handle8834571

    CAS  PubMed  Google Scholar 

  29. H Pelletier JM Millot B Chauffert et al. (1990) ArticleTitleMechanisms of resistance of confluent human and rat colon cancer cells to anthracyclines: alteration of drug passive diffusion Cancer Res. 50 6626–6631 Occurrence Handle1:CAS:528:DyaK3cXmt1Cht7g%3D Occurrence Handle2208125

    CAS  PubMed  Google Scholar 

  30. S Kunimoto K Miura Y Takahashi et al. (1983) ArticleTitleRapid uptake by cultured tumor cells and intracellular behavior of 4’-O-tetrahydropyranyl-adriamycin J. Antibiot. 36 312–317 Occurrence Handle1:CAS:528:DyaL3sXhvFWhsLo%3D Occurrence Handle6833151

    CAS  PubMed  Google Scholar 

  31. H Tapiero JN Munck A Fourcade (1986) ArticleTitleRelationship between the intracellular accumulation of anthracyclines and effectiveness in vitro and in vivo Drugs Exp. Clin. Res. 12 257–264 Occurrence Handle1:STN:280:BimB2svgs1U%3D Occurrence Handle3460752

    CAS  PubMed  Google Scholar 

  32. J Robert A Monnier N Poutignat et al. (1991) ArticleTitleA pharmacokinetic and pharmacodynamic study of the new anthracycline pirarubicin in breast cancer patients Cancer Chemother. Pharmacol. 29 75–79 Occurrence Handle1:STN:280:By2D2snlsVY%3D Occurrence Handle1742853

    CAS  PubMed  Google Scholar 

  33. JN Munck M Riggi R Rougier et al. (1993) ArticleTitlePharmacokinetic and pharmacodynamic advantages of pirarubicin over adriamycin after intraarterial hepatic administration in the rabbit VX2 tumor model Cancer Res. 53 1550–1554 Occurrence Handle1:CAS:528:DyaK3sXit1Cru78%3D Occurrence Handle8453622

    CAS  PubMed  Google Scholar 

  34. P Favoulet JP Cercueil P Faure et al. (2001) ArticleTitleIncreased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma Anticancer. Drugs 12 801–806 Occurrence Handle10.1097/00001813-200111000-00003 Occurrence Handle1:CAS:528:DC%2BD38XjtVCmtw%3D%3D Occurrence Handle11707647

    Article  CAS  PubMed  Google Scholar 

  35. T Okamura Y Ono T Kinukawa et al. (2002) ArticleTitleRandomized study of single early instillation of (2”R)-4’-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma Cancer 94 2363–2368 Occurrence Handle10.1002/cncr.10496.abs Occurrence Handle1:CAS:528:DC%2BD38XktF2hs7c%3D Occurrence Handle12015761

    Article  CAS  PubMed  Google Scholar 

  36. JN Munck P Rougier GG Chabot et al. (1994) ArticleTitlePhase I and pharmacological study of intra-arterial hepatic administration of pirarubicin in patients with advanced hepatic metastases Eur. J. Cancer 30 289–294 Occurrence Handle10.1016/0959-8049(94)90243-7

    Article  Google Scholar 

  37. RF Ozols GY Locker JH Doroshow et al. (1979) ArticleTitlePharmacokinetics of adriamycin and tissue penetration in murine ovarian cancer Cancer Res. 39 3209–3214 Occurrence Handle1:CAS:528:DyaE1MXls1yitr8%3D Occurrence Handle455305

    CAS  PubMed  Google Scholar 

  38. CL Litterst JM Collins MC Lowe et al. (1982) ArticleTitleLocal administration and systemic toxicity resulting from large-volume ip administration of doxorubicin in the rat Cancer Treat. Rep. 66 157–161 Occurrence Handle1:CAS:528:DyaL38XksVE%3D Occurrence Handle7053251

    CAS  PubMed  Google Scholar 

  39. KS Sridhar TS Samy RP Agarwal et al. (1990) ArticleTitleA phase I study of 4’-O-tetrahydropyranyladriamycin: clinical pharmacology and pharmacokinetics Cancer 66 2082–2091 Occurrence Handle1:STN:280:By6D38bgsF0%3D Occurrence Handle2224762

    CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

We thank the French League Against Cancer (Committees of Côte d’Or, Nièvre, and Haute-Marne) and the Inhabitant Committee of Losnes for their grant funding. We thank Jonathan Ewing for his help in revising the manuscript.

Author information

Authors and Affiliations

  1. Unité INSERM 517, Faculty of Medicine, 7 Bd Jeanne d’Arc, 21000, Dijon, France

    Patrick Favoulet M.D., Laurent Benoit M.D., Liliana Osmak M.D., Emmanuel Polycarpe M.D., Philippe Esquis M.D., Christian Duvillard M.D., Boris Guiu & Bruno Chauffert M.D., Ph.D.

  2. Department of Visceral, Thoracic and Oncologic Surgery, University Hospital, 1 Bd Mal Lattre de Tassigny, 21000, Dijon, France

    Patrick Favoulet M.D., Liliana Osmak M.D., Emmanuel Polycarpe M.D., Philippe Esquis M.D., Boris Guiu, Patrick Rat M.D. & Jean Pierre Favre M.D.

  3. Regional Anticancer Centre, 1 Rue du Pr Marion, 21000, Dijon, France

    Laurent Benoit M.D. & Bruno Chauffert M.D., Ph.D.

  4. Department of Head and Neck Surgery, University Hospital, Bd Faubourg Raynes, 21000, Dijon, France

    Christian Duvillard M.D.

Authors
  1. Patrick Favoulet M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurent Benoit M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liliana Osmak M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emmanuel Polycarpe M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Philippe Esquis M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christian Duvillard M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Boris Guiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patrick Rat M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean Pierre Favre M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bruno Chauffert M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Favoulet, P., Benoit, L., Osmak, L. et al. Prevention of Peritoneal Carcinomatosis from Colon Cancer Cell Seeding Using a Pirarubicin Solution in Rats and Nude Mice. World J. Surg. 28, 451–456 (2004). https://doi.org/10.1007/s00268-004-6927-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-004-6927-1

Keywords

Search

Navigation