Abstract
Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 104 colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P=0.05) and of taurolidine/heparin (median 0 mg, P=0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P=0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth and abdominal wound recurrences in rats undergoing midline laparotomy. Neither the intraperitoneal nor the intravenous application or the combination of the two agents influenced the subcutaneous tumor growth. The substances did not alter the changes of peripheral leukocytes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Iwanaka T, Arya G, Ziegler MM. Mechanism and prevention of portsite tumor recurrence after laparoscopy in a murine model. J Pediatr Surg 1998; 33: 457–61.
Neuhaus SJ, Watson DI, Ellis T et al. Efficacy of cytotoxic agents for the prevention of laparoscopic port—site metastases. Arch Surg 1998; 133: 762–6.
Neuhaus SJ, Watson DI, Ellis T et al. Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy. Dis Colon Rectum 1999; 42: 10–5.
Stuntz M, Wilmoth G, Ong J et al. Use of intraperitoneal 5—fluorouracil and chlorhexidine for prevention of recurrence of perforated colorectal carcinoma in a rat model. Dis Colon Rectum 1997; 40: 1085–8.
Wu JS, Pfister SM, Ruiz MB et al. Local treatment of abdominal wound reduces tumor implantation. J Surg Oncol 1998; 69: 9–13.
Jacobi CA, Sabat R, Ordemann J et al. Peritoneale Instillation von Taurolidin und Heparin zur Verhinderung von intraperitonealem Tumorwachstum und Trokarmetastasen bei laparoskopischen Operationen im Rattenmodell. Langenbecks Arch Chir 1997; 382: 31–6.
McCourt M, Wang JH, Sookhai S et al. Taurolidine inhibits tumor cell growth in vitro and in vivo. Ann Surg Oncol 2000; 7: 685–91.
Bedrosian I, Sofia RD, Wolff SM et al. Taurolidine. An analogue of the amino acid taurine, suppresses interleukin–1 and tumor necrosis factor synthesis in human peripheral blood mononuclear cells. Cytokine 1991; 3: 568–75.
Lanfrancone L, Boraschi D, Ghiara P. Human peritoneal mesothelial cells produce many cytokines (granulocyte colony—stimulating factor, granulocyte—monocyte CSF, macrophage CSF, IL–1 and IL–2) and are activated and stimulated to grow by IL–1. Blood 1992; 80: 2835–42.
Yanagisawa M, Imai H, Fukushima Y. Effects on tumour necrosis factor alpha and interleukin 1 beta on the proliferation of cultured glomerular epithelial cells. Virchows Arch 1994; 426: 581–6.
Jacobi CA, Wildbrett P, Volk T et al. Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model. Surg Endosc 1999; 13: 1021–5.
Jacobi CA, Peter FJ, Wenger FA et al. New therapeutic strategies to avoid intra—and extraperitoneal metastases during laparoscopy: Results of a tumor model in the rat. Dig Surg 1999; 16: 393–5.
Goldstein DS, Lu ML, Hattori T. Inhibition of peritoneal tumor cell implantation: Model for laparoscopic cancer surgery. J Endourol 1993; 7: 237–41.
Knight BI, Skellern GG, Browne MK et al. Peritoneal absorption of the antibacterial and antiendotoxin taurolidine in peritonitis. Br J Clin Pharm 1981; 12: 695–9.
Braumann C, Ordemann J, Wildbrett P et al. Influence of intraperitoneal and systemic application of taurolidine and taurolidine/heparin during laparoscopy on intraperitoneal and subcutaneous tumor growth in rats. Clin Exp Metastasis 2001; 18(7): 547–52.
Jacobi CA, Ordemann J, Bühm B et al. The influence of laparotomy and laparoscopy on tumor growth in a rat model. Surg Endosc 1997; 11: 618–21.
Lee SW, Whelan RL, Southall JC et al. Abdominal wound tumor recurrence after open and laparoscopic—assisted splenectomy in a murine model. Dis Colon Rectum 1998; 41: 824–31.
Neuhaus SJ, Ellis T, Jamieson GG et al. Experimental study of the effect of intraperitoneal heparin on tumour implantation following laparoscopy. Br J Surg 1999; 86: 400–4.
Gorman SP, McCafferty DF, Woolfson AD et al. Reduced adherence of micro—organisms to human mucosal epithelial cells following treatment with taurolin, a novel antimicrobial agent. J Appl Bacteriol 1987; 62: 315–20.
Calabresi P, Goulette FA, Darnowski JW. Taurolidine: Cytotoxic and mechanistic evaluation of a novel antineoplastic agent. Cancer Res. 2001; 61:6816–21.
Pfirrmann RW. Einführung und Übersicht. In: Brückner WL und Pfirrmann RW, Taurolin. Ein neues Konzept zur antimikrobiellen Chemotherapie chirurgischer Infektionen. Munich: Urban und Schwarzenberg 1985; 3–23.
Gill WB, Jones KW, Rugierro KJ. Protective effects of heparin and other sulfated glycosaminoglycans on crystal adhesion to injured urothelium. J Urol 1982; 127: 151–4.
Solberg R, Scholz T, Videm V et al. Heparin coating reduces cell activation and mediator release in an in vitro venovenous bypass model for liver transplantation. Transpl Int 1998; 11: 252–8.
Dudas J, Ramadori G, Knittel T et al. Effect of heparin and liver heparan sulphate on interaction of HepG2—derived transcription factors and their cis—acting elements: Altered potential of hepatocellular carcinoma heparan sulphate. Biochem J 2000;350: 245–51.
Gutt CN, Kim ZG, Gessmann T et al. Hepatic tumour spread of colorectal cancer in a laparoscopic animal model. Surg Endosc 2000; 14: 448–51.
Little D, Regan M, Keane RM et al. Perioperative immune modulation. Surgery 1993; 114: 87–91.
Staubach KH. Adjuvante Peritonitistherapie mit Taurolidin Modulation der Mediator—freisetzung. Langenbecks Arch Chir 1997; 382: 26–30.
Da Costa ML, Redmond HP, Bouchier—Hayes DJ. Taurolidine improves survival by abrogating the accelerated development and proliferation of solid tumors and development of organ metastases from circulating tumor cells released following surgery. J Surg Res 2001; 101: 111–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Braumann, C., Ordemann, J., Kilian, M. et al. Local and systemic chemotherapy with taurolidine and taurolidine/heparin in colon cancer-bearing rats undergoing laparotomy. Clin Exp Metastasis 20, 387–394 (2003). https://doi.org/10.1023/A:1025402919341
Issue Date:
DOI: https://doi.org/10.1023/A:1025402919341