Influence of intraperitoneal and systemic application of taurolidine and taurolidine/heparin during laparoscopy on intraperitoneal and subcutaneous tumour growth in rats.
BACKGROUND
Recent clinical and experimental studies investigated the problem and possible pathomechanisms of portsite metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far.


METHODS
After subcutaneous and intraperitoneal injection of 10(4) cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy. two hours, two days. seven days, and four weeks after operation, and the peripheral lymphocytes were determined.


RESULTS
Intraperitoneal (ip) tumour weight in rats receiving taurolidine (median 7 mg) and taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) (P = 0.001). There was no difference of subcutaneus tumour growth among the groups (P = 0.4). Trocar recurrences were decreased when taurolidine was applied ip (3115). ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia.


CONCLUSIONS
The intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.
Braumann
C
C
Department of General, Visceral, Vascular and Thoracic Surgery Humboldt University of Berlin, Charité, Germany.
Ordemann
J
J
Wildbrett
P
P
Jacobi
C A
CA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D010535:Laparoscopy / Q000009:adverse effects*; D008231:Lymphopenia / Q000209:etiology; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D051381:Rats; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013829:Thiadiazines / Q000008:administration & dosage / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine; D006493:Heparin